Skip to main content
SpringerLink
Log in

Molecular genetic landscape of hereditary hearing loss in Pakistan

  • Review
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

Approximately 14.5 million Pakistani individuals have a hearing loss and half of these cases may be due to genetic causes. Though significant progress has been made in uncovering genetic variants for recessively inherited nonsyndromic deafness, Pendred syndrome, and Usher syndromes, the same is not true for dominantly inherited hearing loss, most syndromic cases and deafness with complex inheritance patterns. Variants of 57 genes have been reported to cause nonsyndromic recessive deafness in Pakistan, though most are rare. Variants of just five genes GJB2, HGF, MYO7A, SLC26A4, and TMC1 together explain 57% of profound deafness while those of GJB2, MYO15A, OTOF, SLC26A4, TMC1, and TMPRSS3 account for 47% of moderate to severe hearing loss. In contrast, although variants of at least 39 genes have been implicated in different deafness syndromes, their prevalence in the population and the spectrum of mutations have not been explored. Furthermore, research on genetics of deafness has mostly focused on individuals from the Punjab province and needs to be extended to other regions of Pakistan. Identifying the genes and their variants causing deafness in all ethnic groups is important as it will pinpoint rare as well as recurrent mutations. This information may ultimately help in offering genetic counseling and future treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

accessed from Supplementary Tables 1 and 2

Fig. 3

accessed from Supplementary Tables 1 and 2

Similar content being viewed by others

Availability of data and material

Not applicable.

Code availability

Not applicable.

References

  • Abdelhadi O, Iancu D, Tekman M, Stanescu H, Bockenhauer D, Kleta R (2016) Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome. Mol Genet Genomic Med 4:521–526. https://doi.org/10.1002/mgg3.227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed ZM, Riazuddin S, Wilcox ER (2003) The molecular genetics of Usher syndrome. Clin Genet 63:431–444. https://doi.org/10.1034/j.1399-0004.2003.00109.x

    Article  CAS  PubMed  Google Scholar 

  • Ahmed ZM, Li XC, Powell SD, Riazuddin S, Young TL, Ramzan K, Ahmad Z, Luscombe S, Dhillon K, MacLaren L, Ploplis B, Shotland LI, Ives E, Friedman TB, Morell RJ, Wilcox ER (2004) Characterization of a new full length TMPRSS3 isoform and identification of mutant alleles responsible for nonsyndromic recessive deafness in Newfoundland and Pakistan. BMC Med Genet 5:24. https://doi.org/10.1186/1471-2350-5-24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ahmed S, Sheraz S, Malik SA, Ahmed NR, Farooq S, Raheem A, Basheer F, Nayyar ZA (2018) Frequency of congenital hearing loss in neonates. J Ayub Med Coll Abbottabad 30:234–236

    PubMed  Google Scholar 

  • Ahmed AN, Tahir R, Khan N, Ahmad M, Dawood M, Basit A, Yasin M, Nowshid M, Marwan M, Sultan K, Saleha S (2021) USH2A gene variants cause Keratoconus and Usher syndrome phenotypes in Pakistani families. BMC Ophthalmol 21:191. https://doi.org/10.1186/s12886-021-01957-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akram B, Bashir R (2014) Special education and deaf children in Pakistan: an overview. J Element Educ 22:33–44

    Google Scholar 

  • Ali RH, Shah K, Nasir A, Steyaert W, Coucke PJ, Ahmad W (2016) Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome. Clin Genet 90:263–269. https://doi.org/10.1111/cge.12700

    Article  CAS  PubMed  Google Scholar 

  • Alkhater RA, Ahonen S, Minassian BA (2021) SUCLA2 Arg407Trp mutation can cause a nonprogressive movement disorder - deafness syndrome. Ann Clin Transl Neurol 8:252–258. https://doi.org/10.1002/acn3.51247

    Article  CAS  PubMed  Google Scholar 

  • Alvarez A, del Castillo I, Villamar M, Aguirre LA, Gonzalez-Neira A, Lopez-Nevot A, Moreno-Pelayo MA, Moreno F (2005) High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss. Am J Med Genet A 137A:255–258. https://doi.org/10.1002/ajmg.a.30884

    Article  PubMed  Google Scholar 

  • Anjum S, Azhar A, Tariq M, Baig SM, Bolz HJ, Qayyum M, Naqvi MS, Raja GK (2014) GJB2 gene mutations causing hearing loss in consanguineous Pakistani families. Pak J Life Soc Sci 12:126–131

    Google Scholar 

  • Anwar S, Riazuddin S, Ahmed ZM, Tasneem S, Ateeq ul J, Khan SY, Griffith AJ, Friedman TB (2009) SLC26A4 mutation spectrum associated with DFNB4 deafness and Pendred’s syndrome in Pakistanis. J Hum Genet 54:266–270. https://doi.org/10.1038/jhg.2009.21

    Article  CAS  PubMed  Google Scholar 

  • Atik T, Onay H, Aykut A, Bademci G, Kirazli T, Tekin M, Ozkinay F (2015) Comprehensive analysis of deafness genes in families with autosomal recessive nonsyndromic hearing loss. PLoS ONE 10:e0142154. https://doi.org/10.1371/journal.pone.0142154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baig SM, Koschak A, Lieb A, Gebhart M, Dafinger C, Nürnberg G, Ali A, Ahmad I, Sinnegger-Brauns MJ, Brandt N, Engel J, Mangoni ME, Farooq M, Khan HU, Nürnberg P, Striessnig J, Bolz HJ (2011) Loss of Ca(v)1.3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nat Neurosci 14:77–84. https://doi.org/10.1038/nn.2694

    Article  CAS  PubMed  Google Scholar 

  • Bashir R, Fatima A, Naz S (2010) Mutations in CLDN14 are associated with different hearing thresholds. J Hum Genet 55:767–770. https://doi.org/10.1038/jhg.2010.104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bashir R, Imtiaz A, Fatima A, Alam A, Naz S (2013a) The c.42_52del11 mutation in TPRN and progressive hearing loss in a family from Pakistan. Biochem Genet 51:350–357. https://doi.org/10.1007/s10528-013-9568-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bashir ZE, Latief N, Belyantseva IA, Iqbal F, Riazuddin SA, Khan SN, Friedman TB, Riazuddin S (2013b) Phenotypic variability of CLDN14 mutations causing DFNB29 hearing loss in the Pakistani population. J Hum Genet 58:102–108. https://doi.org/10.1038/jhg.2012.143

    Article  CAS  PubMed  Google Scholar 

  • Battelino S, Klancar G, Kovac J, Battelino T, Trebusak Podkrajsek K (2016) TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss. Eur Arch Otorhinolaryngol 273:1151–1154. https://doi.org/10.1007/s00405-015-3671-0

    Article  PubMed  Google Scholar 

  • Ben Saïd M, Hmani-Aifa M, Amar I, Baig SM, Mustapha M, Delmaghani S, Tlili A, Ghorbel A, Ayadi H, Van Camp G, Smith RJ, Tekin M, Masmoudi S (2010) High frequency of the p. R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects. Genet Test Mol Biomarkers 14:307–311. https://doi.org/10.1089/gtmb.2009.0174

    Article  CAS  PubMed  Google Scholar 

  • Bond J, Flintoff K, Higgins J, Scott S, Bennet C, Parsons J, Mannon J, Jafri H, Rashid Y, Barrow M, Trembath R, Woodruff G, Rossa E, Lynch S, Sheilds J, Newbury-Ecob R, Falconer A, Holland P, Cockburn D, Karbani G, Malik S, Ahmed M, Roberts E, Taylor G, Woods CG (2005) The importance of seeking ALMS1 mutations in infants with dilated cardiomyopathy. J Med Genet 42:e10. https://doi.org/10.1136/jmg.2004.026617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bork JM, Peters LM, Riazuddin S, Bernstein SL, Ahmed ZM, Ness SL, Polomeno R, Ramesh A, Schloss M, Srisailpathy CR, Wayne S, Bellman S, Desmukh D, Ahmed Z, Khan SN, Kaloustian VM, Li XC, Lalwani A, Bitner-Glindzicz M, Nance WE, Liu XZ, Wistow G, Smith RJ, Griffith AJ, Wilcox ER, Friedman TB, Morell RJ (2001) Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 68:26–37. https://doi.org/10.1086/316954

    Article  CAS  PubMed  Google Scholar 

  • Brown KA, Janjua AH, Karbani G, Parry G, Noble A, Crockford G, Bishop DT, Newton VE, Markham AF, Mueller RF (1996) Linkage studies of non-syndromic recessive deafness (NSRD) in a family originating from the Mirpur region of Pakistan maps DFNB1 centromeric to D13S175. Hum Mol Genet 5:169–173. https://doi.org/10.1093/hmg/5.1.169

    Article  CAS  PubMed  Google Scholar 

  • Bukhari I, Mujtaba G, Naz S (2013) Contribution of GJB2 mutations to hearing loss in the Hazara Division of Pakistan. Biochem Genet 51:524–529. https://doi.org/10.1007/s10528-013-9583-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, Buhas D, Mesli S, Naess K, Born AP, Woldseth B, Prontera P, Batbayli M, Ravn K, Joensen F, Cordelli DM, Santorelli FM, Tulinius M, Darin N, Duno M, Jouvencel P, Burlina A, Stangoni G, Bertini E, Redonnet-Vernhet I, Wibrand F, Dionisi-Vici C, Uusimaa J, Vieira P, Osorio AN, McFarland R, Taylor RW, Holme E, Ostergaard E (2016) Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients. J Inherit Metab Dis 39:243–252. https://doi.org/10.1007/s10545-015-9894-9

    Article  CAS  PubMed  Google Scholar 

  • Chen S, Dong C, Wang Q, Zhong Z, Qi Y, Ke X, Liu Y (2016) Targeted next-generation sequencing successfully detects causative genes in Chinese patients with hereditary hearing loss. Genet Test Mol Biomarkers 20:660–665. https://doi.org/10.1089/gtmb.2016.0051

    Article  CAS  PubMed  Google Scholar 

  • Chiereghin C, Robusto M, Mauri L, Primignani P, Castorina P, Ambrosetti U, Duga S, Asselta R, Soldà G (2021) SLC22A4 gene in hereditary non-syndromic hearing loss: recurrence and incomplete penetrance of the p.C113Y mutation in Northwest Africa. Front Genet 12:606630. https://doi.org/10.3389/fgene.2021.606630

  • Choi BY, Ahmed ZM, Riazuddin S, Bhinder MA, Shahzad M, Husnain T, Griffith AJ, Friedman TB (2009) Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan. Clin Genet 75:237–243. https://doi.org/10.1111/j.1399-0004.2008.01128.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coningham R, Young R (2015) The archaeology of South Asia: from the Indus to Asoka, ca. 6500 BCE-200 CE. Cambridge University Press, UK

    Book  Google Scholar 

  • Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC (1998) Molecular analysis of the PDS gene in Pendred syndrome. Hum Mol Genet 7:1105–1112. https://doi.org/10.1093/hmg/7.7.1105

    Article  CAS  PubMed  Google Scholar 

  • Cross JH, Arora R, Heckemann RA, Gunny R, Chong K, Carr L, Baldeweg T, Differ AM, Lench N, Varadkar S, Sirimanna T, Wassmer E, Hulton SA, Ognjanovic M, Ramesh V, Feather S, Kleta R, Hammers A, Bockenhauer D (2013) Neurological features of epilepsy, ataxia, sensorineural deafness, tubulopathy syndrome. Dev Med Child Neurol 55:846–856. https://doi.org/10.1111/dmcn.12171

    Article  PubMed  PubMed Central  Google Scholar 

  • Doll J, Vona B, Schnapp L, Rüschendorf F, Khan I, Khan S, Muhammad N, Alam Khan S, Nawaz H, Khan A, Ahmad N, Kolb SM, Kühlewein L, Labonne JDJ, Layman LC, Hofrichter MAH, Röder T, Dittrich M, Müller T, Graves TD, Kong IK, Nanda I, Kim HG, Haaf T (2020) Genetic spectrum of syndromic and non-syndromic hearing loss in Pakistani families. Genes (basel). https://doi.org/10.3390/genes11111329

    Article  Google Scholar 

  • Elahi MM, Elahi F, Elahi A, Elahi SB (1998) Paediatric hearing loss in rural Pakistan. J Otolaryngol 27:348–353

    CAS  PubMed  Google Scholar 

  • Faridi R, Rehman AU, Morell RJ, Friedman PL, Demain L, Zahra S, Khan AA, Tohlob D, Assir MZ, Beaman G, Khan SN, Newman WG, Riazuddin S, Friedman TB (2017) Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome. Clin Genet 91:328–332. https://doi.org/10.1111/cge.12867

    Article  CAS  PubMed  Google Scholar 

  • Faridi R, Tona R, Brofferio A, Hoa M, Olszewski R, Schrauwen I, Assir MZK, Bandesha AA, Khan AA, Rehman AU, Brewer C, Ahmed W, Leal SM, Riazuddin S, Boyden SE, Friedman TB (2019) Mutational and phenotypic spectra of KCNE1 deficiency in Jervell and Lange-Nielsen Syndrome and Romano-Ward Syndrome. Hum Mutat 40:162–176. https://doi.org/10.1002/humu.23689

    Article  CAS  PubMed  Google Scholar 

  • Faridi R, Rea A, Fenollar-Ferrer C, O’Keefe RT, Gu S, Munir Z, Khan AA, Riazuddin S, Hoa M, Naz S, Newman WG, Friedman TB (2021) New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder. Hum Genet (accepted)

  • Green P, Wiseman M, Crow YJ, Houlden H, Riphagen S, Lin JP, Raymond FL, Childs AM, Sheridan E, Edwards S, Josifova DJ (2010) Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. Am J Hum Genet 86:485–489. https://doi.org/10.1016/j.ajhg.2010.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hussain R, Bittles AH (1998) The prevalence and demographic characteristics of consanguineous marriages in Pakistan. J Biosoc Sci 30:261–275. https://doi.org/10.1017/s0021932098002612

    Article  CAS  PubMed  Google Scholar 

  • Imtiaz A, Maqsood A, Rehman AU, Morell RJ, Holt JR, Friedman TB, Naz S (2016) Recessive mutations of TMC1 associated with moderate to severe hearing loss. Neurogenetics 17:115–123. https://doi.org/10.1007/s10048-016-0477-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imtiaz A, Belyantseva IA, Beirl AJ, Fenollar-Ferrer C, Bashir R, Bukhari I, Bouzid A, Shaukat U, Azaiez H, Booth KT, Kahrizi K, Najmabadi H, Maqsood A, Wilson EA, Fitzgerald TS, Tlili A, Olszewski R, Lund M, Chaudhry T, Rehman AU, Starost MF, Waryah AM, Hoa M, Dong L, Morell RJ, Smith RJH, Riazuddin S, Masmoudi S, Kindt KS, Naz S, Friedman TB (2018) CDC14A phosphatase is essential for hearing and male fertility in mouse and human. Hum Mol Genet 27:780–798. https://doi.org/10.1093/hmg/ddx440

    Article  CAS  PubMed  Google Scholar 

  • Iqbal H, Sarfaraz T, Anjum F, Anwar Z, Mir A (2011) Identification of missense mutation (I12T) in the BSND gene and bioinformatics analysis. J Biomed Biotechnol 2011:304612. https://doi.org/10.1155/2011/304612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jabeen R, Babar ME, Ahmad J, Awan AR (2012) Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome. Mol Biol Rep 39:785–788. https://doi.org/10.1007/s11033-011-0799-x

    Article  CAS  PubMed  Google Scholar 

  • Jenkinson EM, Rehman AU, Walsh T, Clayton-Smith J, Lee K, Morell RJ, Drummond MC, Khan SN, Naeem MA, Rauf B, Billington N, Schultz JM, Urquhart JE, Lee MK, Berry A, Hanley NA, Mehta S, Cilliers D, Clayton PE, Kingston H, Smith MJ, Warner TT, Black GC, Trump D, Davis JR, Ahmad W, Leal SM, Riazuddin S, King MC, Friedman TB, Newman WG (2013) Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. Am J Hum Genet 92:605–613. https://doi.org/10.1016/j.ajhg.2013.02.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM (1997) Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature 387:80–83. https://doi.org/10.1038/387080a0

    Article  CAS  PubMed  Google Scholar 

  • Khan A, Han S, Wang R, Ansar M, Ahmad W, Zhang X (2019) Sequence variants in genes causing nonsyndromic hearing loss in a Pakistani cohort. Mol Genet Genomic Med 7:e917. https://doi.org/10.1002/mgg3.917

    Article  PubMed  PubMed Central  Google Scholar 

  • Kurima K, Peters LM, Yang Y, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo J, Makishima T, Ghosh M, Menon PS, Deshmukh D, Oddoux C, Ostrer H, Khan S, Deininger PL, Hampton LL, Sullivan SL, Battey JF Jr, Keats BJ, Wilcox ER, Friedman TB, Griffith AJ (2002) Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30:277–284. https://doi.org/10.1038/ng842

    Article  PubMed  Google Scholar 

  • Lee K, Khan S, Islam A, Ansar M, Andrade PB, Kim S, Santos-Cortez RL, Ahmad W, Leal SM (2012) Novel TMPRSS3 variants in Pakistani families with autosomal recessive non-syndromic hearing impairment. Clin Genet 82:56–63. https://doi.org/10.1111/j.1399-0004.2011.01695.x

    Article  CAS  PubMed  Google Scholar 

  • Liaqat K, Schrauwen I, Raza SI, Lee K, Hussain S, Chakchouk I, Nasir A, Acharya A, Abbe I, Umair M, Ansar M, Ullah I, Shah K, Bamshad MJ, Nickerson DA, Ahmad W, Leal SM (2019) Identification of CACNA1D variants associated with sinoatrial node dysfunction and deafness in additional Pakistani families reveals a clinical significance. J Hum Genet 64:153–160. https://doi.org/10.1038/s10038-018-0542-8

    Article  CAS  PubMed  Google Scholar 

  • Mašindová I, Šoltýsová A, Varga L, Mátyás P, Ficek A, Hučková M, Sůrová M, Šafka-Brožková D, Anwar S, Bene J, Straka S, Janicsek I, Ahmed ZM, Seeman P, Melegh B, Profant M, Klimeš I, Riazuddin S, Kádasi Ľ, Gašperíková D (2015) MARVELD2 (DFNB49) mutations in the hearing impaired Central European Roma population—prevalence, clinical impact and the common origin. PLoS ONE 10:e0124232. https://doi.org/10.1371/journal.pone.0124232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mei X, Zhou Y, Amjad M, Yang W, Zhu R, Asif M, Hussain HMJ, Yang T, Iqbal F, Hu H (2021) Next-generation sequencing identifies pathogenic variants in HGF, POU3F4, TECTA, and MYO7A in consanguineous Pakistani deaf families. Neural Plast 2021:5528434. https://doi.org/10.1155/2021/5528434

  • Mersch J, Brown N, Pirzadeh-Miller S, Mundt E, Cox HC, Brown K, Aston M, Esterling L, Manley S, Ross T (2018) Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA 320:1266–1274. https://doi.org/10.1001/jama.2018.13152

    Article  PubMed  PubMed Central  Google Scholar 

  • Metspalu M, Mondal M, Chaubey G (2018) The genetic makings of South Asia. Curr Opin Genet Dev 53:128–133. https://doi.org/10.1016/j.gde.2018.09.003

    Article  CAS  PubMed  Google Scholar 

  • Monzó C, Gimeno- Ferrer F, García JCF, Amadoz A, Albuquerque D, Angueira FB, Marcaida G, Rodríguez- López R (2017) Alström syndrome caused by deletion in ALMS1 gene fixed in a Northern Pakistan recurrent haplotype. Indian J Case Rep 3:171–174

    Article  Google Scholar 

  • Morell RJ, Olszewski R, Tona R, Leitess S, Wafa TT, Taukulis I, Schultz JM, Thomason EJ, Richards K, Whitley BN, Hill C, Saunders T, Starost MF, Fitzgerald T, Wilson E, Ohyama T, Friedman TB, Hoa M (2020) Noncoding microdeletion in mouse Hgf disrupts neural crest migration into the stria vascularis, reduces the endocochlear potential, and suggests the neuropathology for human nonsyndromic deafness DFNB39. J Neurosci 40:2976–2992. https://doi.org/10.1523/JNEUROSCI.2278-19.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mumtaz N, Babur MN, Saqulain G (2019) Multi-level barriers & priorities accorded by policy makers for neonatal hearing screening (NHS) in Pakistan: a thematic analysis. Pak J Med Sci 35:1674–1679. https://doi.org/10.12669/pjms.35.6.703

    Article  PubMed  PubMed Central  Google Scholar 

  • Narasimhan VM, Patterson N, Moorjani P, Rohland N, Bernardos R, Mallick S et al (2019) The formation of human populations in South and Central Asia. Science. https://doi.org/10.1126/science.aat7487

    Article  PubMed  PubMed Central  Google Scholar 

  • Nayak G, Varga L, Trincot C, Shahzad M, Friedman PL, Klimes I, Greinwald JH Jr, Riazuddin SA, Masindova I, Profant M, Khan SN, Friedman TB, Ahmed ZM, Gasperikova D, Riazuddin S (2015) Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss. Hum Genet 134:423–437. https://doi.org/10.1007/s00439-015-1532-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naz S, Alasti F, Mowjoodi A, Riazuddin S, Sanati MH, Friedman TB, Griffith AJ, Wilcox ER (2003) Distinctive audiometric profile associated with DFNB21 alleles of TECTA. J Med Genet 40:360–363. https://doi.org/10.1136/jmg.40.5.360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naz S, Imtiaz A, Mujtaba G, Maqsood A, Bashir R, Bukhari I, Khan MR, Ramzan M, Fatima A, Rehman AU, Iqbal M, Chaudhry T, Lund M, Brewer CC, Morell RJ, Friedman TB (2017) Genetic causes of moderate to severe hearing loss point to modifiers. Clin Genet 91:589–598. https://doi.org/10.1111/cge.12856

    Article  CAS  PubMed  Google Scholar 

  • Neuhaus C, Eisenberger T, Decker C, Nagl S, Blank C, Pfister M, Kennerknecht I, Muller-Hofstede C, Charbel Issa P, Heller R, Beck B, Ruther K, Mitter D, Rohrschneider K, Steinhauer U, Korbmacher HM, Huhle D, Elsayed SM, Taha HM, Baig SM, Stohr H, Preising M, Markus S, Moeller F, Lorenz B, Nagel-Wolfrum K, Khan AO, Bolz HJ (2017) Next-generation sequencing reveals the mutational landscape of clinically diagnosed Usher syndrome: copy number variations, phenocopies, a predominant target for translational read-through, and PEX26 mutated in Heimler syndrome. Mol Genet Genomic Med 5:531–552. https://doi.org/10.1002/mgg3.312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ng YS, Alston CL, Diodato D, Morris AA, Ulrick N, Kmoch S, Houštěk J, Martinelli D, Haghighi A, Atiq M, Gamero MA, Garcia-Martinez E, Kratochvílová H, Santra S, Brown RM, Brown GK, Ragge N, Monavari A, Pysden K, Ravn K, Casey JP, Khan A, Chakrapani A, Vassallo G, Simons C, McKeever K, O’Sullivan S, Childs AM, Østergaard E, Vanderver A, Goldstein A, Vogt J, Taylor RW, McFarland R (2016) The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. J Med Genet 53:768–775. https://doi.org/10.1136/jmedgenet-2016-103910

    Article  CAS  PubMed  Google Scholar 

  • Nikopoulos K, Butt GU, Farinelli P, Mudassar M, Domenech-Estevez E, Samara C, Kausar M, Masroor I, Chrast R, Rivolta C, Siddiqi S (2016) A large multiexonic genomic deletion within the ALMS1 gene causes Alstrom syndrome in a consanguineous Pakistani family. Clin Genet 89:510–511. https://doi.org/10.1111/cge.12645

    Article  CAS  PubMed  Google Scholar 

  • Noman M, Ishaq R, Bukhari SA, Ahmed ZM, Riazuddin S (2019) Delineation of homozygous variants associated with prelingual sensorineural hearing loss in Pakistani families. Genes (basel). https://doi.org/10.3390/genes10121031

    Article  Google Scholar 

  • Olsen BS, Hahnemann JM, Schwartz M, Østergaard E (2007) Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood. Pediatr Diabetes 8:239–241. https://doi.org/10.1111/j.1399-5448.2007.00251.x

    Article  PubMed  Google Scholar 

  • Oonk AM, Huygen PL, Kunst HP, Kremer H, Pennings RJ (2016) Features of autosomal recessive non-syndromic hearing impairment: a review to serve as a reference. Clin Otolaryngol 41:487–497. https://doi.org/10.1111/coa.12567

    Article  CAS  PubMed  Google Scholar 

  • Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Griffith AJ (2003) Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet 40:242–248. https://doi.org/10.1136/jmg.40.4.242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park HR, Kanwal S, Lim SO, Nam DE, Choi YJ, Chung KW (2020) Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss. Mol Biol Rep 47:9979–9985. https://doi.org/10.1007/s11033-020-06037-7

    Article  CAS  PubMed  Google Scholar 

  • Ramzan M, Bashir R, Salman M, Mujtaba G, Sobreira N, Witmer PD, Naz S (2020) Spectrum of genetic variants in moderate to severe sporadic hearing loss in Pakistan. Sci Rep 10:11902. https://doi.org/10.1038/s41598-020-68779-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raz T, Labay V, Baron D, Szargel R, Anbinder Y, Barrett T, Rabl W, Viana MB, Mandel H, Baruchel A, Cayuela JM, Cohen N (2000) The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families. Hum Mutat 16:37–42. https://doi.org/10.1002/1098-1004(200007)16:1%3c37::AID-HUMU7%3e3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  • Rehman AU, Morell RJ, Belyantseva IA, Khan SY, Boger ET, Shahzad M, Ahmed ZM, Riazuddin S, Khan SN, Friedman TB (2010) Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79. Am J Hum Genet 86:378–388. https://doi.org/10.1016/j.ajhg.2010.01.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rehman AU, Santos-Cortez RL, Morell RJ, Drummond MC, Ito T, Lee K, Khan AA, Basra MA, Wasif N, Ayub M, Ali RA, Raza SI, Nickerson DA, Shendure J, Bamshad M, Riazuddin S, Billington N, Khan SN, Friedman PL, Griffith AJ, Ahmad W, Leal SM, Friedman TB (2014) Mutations in TBC1D24, a gene associated with epilepsy, also cause nonsyndromic deafness DFNB86. Am J Hum Genet 94:144–152. https://doi.org/10.1016/j.ajhg.2013.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rehman AU, Santos-Cortez RL, Drummond MC, Shahzad M, Lee K, Morell RJ, Ansar M, Jan A, Wang X, Aziz A, Riazuddin S, Smith JD, Wang GT, Ahmed ZM, Gul K, Shearer AE, Smith RJ, Shendure J, Bamshad MJ, Nickerson DA, Hinnant J, Khan SN, Fisher RA, Ahmad W, Friderici KH, Friedman TB, Wilch ES, Leal SM (2015) Challenges and solutions for gene identification in the presence of familial locus heterogeneity. Eur J Hum Genet 23:1207–1215. https://doi.org/10.1038/ejhg.2014.266

    Article  CAS  PubMed  Google Scholar 

  • Riazuddin S, Ahmed ZM, Fanning AS, Lagziel A, Kitajiri S, Ramzan K, Khan SN, Chattaraj P, Friedman PL, Anderson JM, Belyantseva IA, Forge A, Friedman TB (2006) Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet 79:1040–1051. https://doi.org/10.1086/510022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riazuddin S, Nazli S, Ahmed ZM, Yang Y, Zulfiqar F, Shaikh RS, Zafar AU, Khan SN, Sabar F, Javid FT, Wilcox ER, Tsilou E, Boger ET, Sellers JR, Belyantseva IA, Friedman TB (2008) Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function. Hum Mutat 29:502–511. https://doi.org/10.1002/humu.20677

    Article  CAS  PubMed  Google Scholar 

  • Riazuddin S, Anwar S, Fischer M, Ahmed ZM, Khan SY, Janssen AG, Zafar AU, Scholl U, Husnain T, Belyantseva IA, Friedman PL, Friedman TB, Fahlke C (2009) Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. Am J Hum Genet 85:273–280. https://doi.org/10.1016/j.ajhg.2009.07.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riazuddin S, Ahmed ZM, Hegde RS, Khan SN, Nasir I, Shaukat U, Butman JA, Griffith AJ, Friedman TB, Choi BY (2011) Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome. BMC Med Genet 12:21. https://doi.org/10.1186/1471-2350-12-21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Riazuddin S, Belyantseva IA, Giese AP, Lee K, Indzhykulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andrade-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan SN, Akram J, Tekin M, Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM (2012) Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet 44:1265–1271. https://doi.org/10.1038/ng.2426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richard EM, Santos-Cortez RLP, Faridi R, Rehman AU, Lee K, Shahzad M, Acharya A, Khan AA, Imtiaz A, Chakchouk I, Takla C, Abbe I, Rafeeq M, Liaqat K, Chaudhry T, Bamshad MJ, Nickerson DA, Schrauwen I, Khan SN, Morell RJ, Zafar S, Ansar M, Ahmed ZM, Ahmad W, Riazuddin S, Friedman TB, Leal SM (2019) Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss. Hum Mutat 40:53–72. https://doi.org/10.1002/humu.23666

    Article  CAS  PubMed  Google Scholar 

  • Rickard S, Kelsell DP, Sirimana T, Rajput K, MacArdle B, Bitner-Glindzicz M (2001) Recurrent mutations in the deafness gene GJB2 (connexin 26) in British Asian families. J Med Genet 38:530–533. https://doi.org/10.1136/jmg.38.8.530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rothrock CR, Murgia A, Sartorato EL, Leonardi E, Wei S, Lebeis SL, Yu LE, Elfenbein JL, Fisher RA, Friderici KH (2003) Connexin 26 35delG does not represent a mutational hotspot. Hum Genet 113:18–23. https://doi.org/10.1007/s00439-003-0944-2

    Article  CAS  PubMed  Google Scholar 

  • Roux AF, Faugere V, Vache C, Baux D, Besnard T, Leonard S, Blanchet C, Hamel C, Mondain M, Gilbert-Dussardier B, Edery P, Lacombe D, Bonneau D, Holder-Espinasse M, Ambrosetti U, Journel H, David A, Lina-Granade G, Malcolm S, Claustres M (2011) Four-year follow-up of diagnostic service in USH1 patients. Invest Ophthalmol vis Sci 52:4063–4071. https://doi.org/10.1167/iovs.10-6869

    Article  PubMed  Google Scholar 

  • Safka Brozkova D, Lastuvkova J, Stepankova H, Krutova M, Trkova M, Myska P, Seeman P (2012) DFNB49 is an important cause of non-syndromic deafness in Czech Roma patients but not in the general Czech population. Clin Genet 82:579–582. https://doi.org/10.1111/j.1399-0004.2011.01817.x

    Article  CAS  PubMed  Google Scholar 

  • Salman M, Bashir R, Imtiaz A, Maqsood A, Mujtaba G, Iqbal M, Naz S (2015) Mutations of GJB2 encoding connexin 26 contribute to non-syndromic moderate and severe hearing loss in Pakistan. Eur Arch Otorhinolaryngol 272:2071–2075. https://doi.org/10.1007/s00405-015-3523-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Santos RL, Wajid M, Pham TL, Hussan J, Ali G, Ahmad W, Leal SM (2005) Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non-syndromic hearing impairment. Clin Genet 67:61–68. https://doi.org/10.1111/j.1399-0004.2005.00379.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrauwen I, Helfmann S, Inagaki A, Predoehl F, Tabatabaiefar MA, Picher MM, Sommen M, Zazo Seco C, Oostrik J, Kremer H, Dheedene A, Claes C, Fransen E, Chaleshtori MH, Coucke P, Lee A, Moser T, Van Camp G (2012) A mutation in CABP2, expressed in cochlear hair cells, causes autosomal-recessive hearing impairment. Am J Hum Genet 91:636–645. https://doi.org/10.1016/j.ajhg.2012.08.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrauwen I, Chakchouk I, Acharya A, Liaqat K, DA Irfanullah N, Bamshad MJ, Shah K, Ahmad W, Leal SM (2018) Novel digenic inheritance of PCDH15 and USH1G underlies profound non-syndromic hearing impairment. BMC Med Genet 19:122. https://doi.org/10.1186/s12881-018-0618-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrauwen I, Liaqat K, Schatteman I, Bharadwaj T, Nasir A, Acharya A, Ahmad W, Van Camp G, Leal SM (2020) Autosomal dominantly inherited GREB1L variants in individuals with profound sensorineural hearing impairment. Genes (basel). https://doi.org/10.3390/genes11060687

    Article  Google Scholar 

  • Schultz JM, Khan SN, Ahmed ZM, Riazuddin S, Waryah AM, Chhatre D, Starost MF, Ploplis B, Buckley S, Velásquez D, Kabra M, Lee K, Hassan MJ, Ali G, Ansar M, Ghosh M, Wilcox ER, Ahmad W, Merlino G, Leal SM, Friedman TB, Morell RJ (2009) Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39. Am J Hum Genet 85:25–39. https://doi.org/10.1016/j.ajhg.2009.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schultz JM, Bhatti R, Madeo AC, Turriff A, Muskett JA, Zalewski CK, King KA, Ahmed ZM, Riazuddin S, Ahmad N, Hussain Z, Qasim M, Kahn SN, Meltzer MR, Liu XZ, Munisamy M, Ghosh M, Rehm HL, Tsilou ET, Griffith AJ, Zein WM, Brewer CC, Friedman TB (2011) Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes. J Med Genet 48:767–775. https://doi.org/10.1136/jmedgenet-2011-100262

    Article  CAS  PubMed  Google Scholar 

  • Scott HS, Kudoh J, Wattenhofer M, Shibuya K, Berry A, Chrast R, Guipponi M, Wang J, Kawasaki K, Asakawa S, Minoshima S, Younus F, Mehdi SQ, Radhakrishna U, Papasavvas MP, Gehrig C, Rossier C, Korostishevsky M, Gal A, Shimizu N, Bonne-Tamir B, Antonarakis SE (2001) Insertion of beta-satellite repeats identifies a transmembrane protease causing both congenital and childhood onset autosomal recessive deafness. Nat Genet 27:59–63. https://doi.org/10.1038/83768

    Article  CAS  PubMed  Google Scholar 

  • Seco CZ, Giese AP, Shafique S, Schraders M, Oonk AM, Grossheim M, Oostrik J, Strom T, Hegde R, van Wijk E, Frolenkov GI, Azam M, Yntema HG, Free RH, Riazuddin S, Verheij JB, Admiraal RJ, Qamar R, Ahmed ZM, Kremer H (2016) Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells. Eur J Hum Genet 24:542–549. https://doi.org/10.1038/ejhg.2015.157

    Article  CAS  PubMed  Google Scholar 

  • Shafique S, Siddiqi S, Schraders M, Oostrik J, Ayub H, Bilal A, Ajmal M, Seco CZ, Strom TM, Mansoor A, Mazhar K, Shah ST, Hussain A, Azam M, Kremer H, Qamar R (2014) Genetic spectrum of autosomal recessive non-syndromic hearing loss in Pakistani families. PLoS ONE 9:e100146. https://doi.org/10.1371/journal.pone.0100146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaikh H, Waryah AM, Narsani AK, Iqbal M, Shahzad M, Waryah YM, Shaikh N, Mahmood A (2017) genetic testing of non-familial deaf patients for CIB2 and GJB2 mutations: phenotype and genetic counselling. Biochem Genet 55:410–420. https://doi.org/10.1007/s10528-017-9828-3

    Article  CAS  PubMed  Google Scholar 

  • Silva M, Oliveira M, Vieira D, Brandao A, Rito T, Pereira JB, Fraser RM, Hudson B, Gandini F, Edwards C, Pala M, Koch J, Wilson JF, Pereira L, Richards MB, Soares P (2017) A genetic chronology for the Indian Subcontinent points to heavily sex-biased dispersals. BMC Evol Biol 17:88. https://doi.org/10.1186/s12862-017-0936-9

    Article  PubMed  PubMed Central  Google Scholar 

  • Sloan-Heggen CM, Babanejad M, Beheshtian M, Simpson AC, Booth KT, Ardalani F, Frees KL, Mohseni M, Mozafari R, Mehrjoo Z, Jamali L, Vaziri S, Akhtarkhavari T, Bazazzadegan N, Nikzat N, Arzhangi S, Sabbagh F, Otukesh H, Seifati SM, Khodaei H, Taghdiri M, Meyer NC, Daneshi A, Farhadi M, Kahrizi K, Smith RJ, Azaiez H, Najmabadi H (2015) Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. J Med Genet 52:823–829. https://doi.org/10.1136/jmedgenet-2015-103389

    Article  CAS  PubMed  Google Scholar 

  • Tariq H, Zaigham K (2019) Genetic contribution of GJB2 gene and DFNB2 locus to hearing impairment in Kashmiri and Pakistani families. Biomed Lett 5:53–66

    Google Scholar 

  • Tona R, Lopez IA, Fenollar-Ferrer C, Faridi R, Anselmi C, Khan AA, Shahzad M, Morell RJ, Gu S, Hoa M, Dong L, Ishiyama A, Belyantseva IA, Riazuddin S, Friedman TB (2020) Mouse models of human pathogenic variants of TBC1D24 associated with non-syndromic deafness DFNB86 and DFNA65 and syndromes involving deafness. Genes (basel). https://doi.org/10.3390/genes11101122

    Article  Google Scholar 

  • Ullah S, Aslamkhan M, Ali A, Idrees M (2017) Causes of deafness in the Punjab region of Pakistan and the role of consanguinity. Public Health 145:93–95. https://doi.org/10.1016/j.puhe.2016.12.019

    Article  CAS  PubMed  Google Scholar 

  • Umair M, Seidel H, Ahmed I, Ullah A, Haack TB, Alhaddad B, Jan A, Rafique A, Strom TM, Ahmad F, Meitinger T, Ahmad W (2017) Ellis-van Creveld syndrome and profound deafness resulted by sequence variants in the EVC/EVC2 and TMC1 genes. J Genet 96:1005–1014. https://doi.org/10.1007/s12041-017-0868-6

    Article  CAS  PubMed  Google Scholar 

  • Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ (2006) OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet 43:576–581. https://doi.org/10.1136/jmg.2005.038612

    Article  CAS  PubMed  Google Scholar 

  • Veske A, Oehlmann R, Younus F, Mohyuddin A, Müller-Myhsok B, Mehdi SQ, Gal A (1996) Autosomal recessive non-syndromic deafness locus (DFNB8) maps on chromosome 21q22 in a large consanguineous kindred from Pakistan. Hum Mol Genet 5:165–168. https://doi.org/10.1093/hmg/5.1.165

    Article  CAS  PubMed  Google Scholar 

  • Wang R, Han S, Khan A, Zhang X (2017) Molecular analysis of twelve Pakistani families with nonsyndromic or syndromic hearing loss. Genet Test Mol Biomarkers 21:316–321. https://doi.org/10.1089/gtmb.2016.0328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waryah AM, Ahmed ZM, Bhinder MA, Choo DI, Sisk RA, Shahzad M, Khan SN, Friedman TB, Riazuddin S (2011) Molecular and clinical studies of X-linked deafness among Pakistani families. J Hum Genet 56:534–540. https://doi.org/10.1038/jhg.2011.55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wattenhofer M, Di Iorio MV, Rabionet R, Dougherty L, Pampanos A, Schwede T, Montserrat-Sentis B, Arbones ML, Iliades T, Pasquadibisceglie A, D’Amelio M, Alwan S, Rossier C, Dahl HH, Petersen MB, Estivill X, Gasparini P, Scott HS, Antonarakis SE (2002) Mutations in the TMPRSS3 gene are a rare cause of childhood nonsyndromic deafness in Caucasian patients. J Mol Med (berl) 80:124–131. https://doi.org/10.1007/s00109-001-0310-6

    Article  CAS  Google Scholar 

  • Weegerink NJ, Schraders M, Oostrik J, Huygen PL, Strom TM, Granneman S, Pennings RJ, Venselaar H, Hoefsloot LH, Elting M, Cremers CW, Admiraal RJ, Kremer H, Kunst HP (2011) Genotype-phenotype correlation in DFNB8/10 families with TMPRSS3 mutations. J Assoc Res Otolaryngol 12:753–766. https://doi.org/10.1007/s10162-011-0282-3

    Article  PubMed  PubMed Central  Google Scholar 

  • Woodcock IR, Menezes MP, Coleman L, Yaplito-Lee J, Peters H, White SM, Stapleton R, Phelan DG, Chong B, Lunke S, Stark Z, Pitt J, Ryan MM, Robertson C, Yiu EM (2018) Genetic, radiologic, and clinical variability in Brown-Vialetto-van Laere Syndrome. Semin Pediatr Neurol 26:2–9. https://doi.org/10.1016/j.spen.2017.03.001

    Article  PubMed  Google Scholar 

  • Yoong SY, Mavrogiannis LA, Wright J, Fairley L, Bennett CP, Charlton RS, Spencer N (2011) Low prevalence of DFNB1 (connexin 26) mutations in British Pakistani children with non-syndromic sensorineural hearing loss. Arch Dis Child 96:798–803. https://doi.org/10.1136/adc.2010.209262

    Article  PubMed  Google Scholar 

  • Yousaf R, Ahmed ZM, Giese AP, Morell RJ, Lagziel A, Dabdoub A, Wilcox ER, Riazuddin S, Friedman TB (2018) Modifier variant of METTL13 suppresses human GAB1-associated profound deafness. J Clin Invest 128:1509–1522. https://doi.org/10.1172/jci97350

    Article  PubMed  PubMed Central  Google Scholar 

  • Zafar S, Shahzad M, Ishaq R, Yousaf A, Shaikh RS, Akram J, Ahmed ZM, Riazuddin S (2020) Novel mutations in CLPP, LARS2, CDH23, and COL4A5 identified in familial cases of prelingual hearing loss. Genes (basel). https://doi.org/10.3390/genes11090978

    Article  Google Scholar 

  • Zaigham K, Tariq H, Qaiser TA, Maqsood SB, Khan AA (2020) Evaluation of a recurrent mutation in HGF gene responsible for non-syndromic hereditary deafness in Kashmiri population. Adv Life Sci 7:281–286

    CAS  Google Scholar 

  • Zheng QY, Scarborough JD, Zheng Y, Yu H, Choi D, Gillespie PG (2012) Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations in other Usher I genes. Hum Mol Genet 21:2588–2598. https://doi.org/10.1093/hmg/dds084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Tariq M, He S, Abdullah U, Zhang J, Baig SM (2020) Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistani families. BMC Med Genet 21:151. https://doi.org/10.1186/s12881-020-01087-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The author expresses her profound gratitude to Sufian Ahmed for illustrating the manuscript and Thomas B Friedman for suggestions. SN was funded by Higher Education Commission, Pakistan (HEC #3288).

Funding

Higher Education Commission, Pakistan (HEC #3288).

Author information

Authors and Affiliations

  1. School of Biological Sciences, University of the Punjab, Quaid-e-Azam Campus, Lahore, 54590, Pakistan

    Sadaf Naz

Authors
  1. Sadaf Naz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SN prepared the manuscript.

Corresponding author

Correspondence to Sadaf Naz.

Ethics declarations

Conflict of interest

None.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 440 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Naz, S. Molecular genetic landscape of hereditary hearing loss in Pakistan. Hum Genet 141, 633–648 (2022). https://doi.org/10.1007/s00439-021-02320-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00439-021-02320-0

Search

Navigation