Abstract
Deafness and onychodystrophy syndromes are a group of phenotypically overlapping syndromes, which include DDOD syndrome (dominant deafness-onychodystrophy), DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and Zimmermann–Laband syndrome (gingival hypertrophy, coarse facial features, hypoplasia or aplasia of nails and terminal phalanges, intellectual disability, and hypertrichosis). Pathogenic variants in four genes, ATP6V1B2, TBC1D24, KCNH1 and KCNN3, have been shown to be associated with deafness and onychodystrophy syndromes. ATP6V1B2 encodes a component of the vacuolar H+-ATPase (V-ATPase) and TBC1D24 belongs to GTPase-activating protein, which are all involved in the regulation of membrane trafficking. The overlapping clinical phenotype of TBC1D24- and ATP6V1B2- related diseases and their function with GTPases or ATPases activity indicate that they may have some physiological link. Variants in genes encoding potassium channels KCNH1 or KCNN3, underlying human Zimmermann–Laband syndrome, have only recently been recognized. Although further analysis will be needed, these findings will help to elucidate an understanding of the pathogenesis of these disorders better and will aid in the development of potential therapeutic approaches. In this review, we summarize the latest developments of clinical features and molecular basis that have been reported to be associated with deafness and onychodystrophy disorders and highlight the challenges that may arise in the differential diagnosis.
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Abbas YM, Wu D, Bueler SA, Robinson CV, Rubinstein JL (2020) Structure of V-ATPase from the mammalian brain. Science 367:1240–1246. https://doi.org/10.1126/science.aaz2924
Alavandar G (1965) Elephantiasis gingivae. Report of an affected family with associated hepatomegaly, soft tissue & skeletal abnormalities. J All India Dent Assoc 37:349–353
Ali RA, Rehman AU, Khan SN, Husnain T, Riazuddin S, Friedman TB, Ahmed ZM (2012) DFNB86, a novel autosomal recessive non-syndromic deafness locus on chromosome 16p13.3. Clin Genet 81:498–500. https://doi.org/10.1111/j.1399-0004.2011.01729.x
Aprile D, Fruscione F, Baldassari S, Fadda M, Ferrante D, Falace A, Buhler E, Sartorelli J, Represa A, Baldelli P, Benfenati F, Zara F, Fassio A (2019) TBC1D24 regulates axonal outgrowth and membrane trafficking at the growth cone in rodent and human neurons. Cell Death Differ 26:2464–2478. https://doi.org/10.1038/s41418-019-0313-x
Atli E, Gurkan H, Ulusal S, Karal Y, Atli EI, Tozkir H (2018) Identification of a novel homozygous TBC1D24 mutation in a Turkish family with DOORS syndrome. Clin Dysmorphol 27:1–3. https://doi.org/10.1097/MCD.0000000000000204
Aubert Mucca M, Patat O, Whalen S, Arnaud L, Barcia G, Buratti J, Cogne B, Doummar D, Karsenty C, Kenis S, Leguern E, Lesca G, Nava C, Nizon M, Piton A, Valence S, Villard L, Weckhuysen S, Keren B, Mignot C (2021) Patients with KCNH1-related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome. J Med Genet. https://doi.org/10.1136/jmedgenet-2020-107511
Azaiez H, Booth KT, Bu F, Huygen P, Shibata SB, Shearer AE, Kolbe D, Meyer N, Black-Ziegelbein EA, Smith RJ (2014) TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss. Hum Mutat 35:819–823. https://doi.org/10.1002/humu.22557
Balestrini S, Milh M, Castiglioni C, Luthy K, Finelli MJ, Verstreken P, Cardon A, Strazisar BG, Holder JL Jr, Lesca G, Mancardi MM, Poulat AL, Repetto GM, Banka S, Bilo L, Birkeland LE, Bosch F, Brockmann K, Cross JH, Doummar D, Felix TM, Giuliano F, Hori M, Huning I, Kayserili H, Kini U, Lees MM, Meenakshi G, Mewasingh L, Pagnamenta AT, Peluso S, Mey A, Rice GM, Rosenfeld JA, Taylor JC, Troester MM, Stanley CM, Ville D, Walkiewicz M, Falace A, Fassio A, Lemke JR, Biskup S, Tardif J, Ajeawung NF, Tolun A, Corbett M, Gecz J, Afawi Z, Howell KB, Oliver KL, Berkovic SF, Scheffer IE, de Falco FA, Oliver PL, Striano P, Zara F, Campeau PM, Sisodiya SM (2016) TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features. Neurology 87:77–85. https://doi.org/10.1212/WNL.0000000000002807
Banuelos E, Ramsey K, Belnap N, Krishnan M, Balak C, Szelinger S, Siniard AL, Russell M, Richholt R, De Both M, Piras I, Naymik M, Claasen AM, Rangasamy S, Huentelman MJ, Craig DW, Campeau PM, Narayanan V, Schrauwen I (2017) Case Report: Novel mutations in TBC1D24 are associated with autosomal dominant tonic-clonic and myoclonic epilepsy and recessive Parkinsonism, psychosis, and intellectual disability. F1000Res 6:553. https://doi.org/10.12688/f1000research.10588.1
Bauer CK, Schneeberger PE, Kortum F, Altmuller J, Santos-Simarro F, Baker L, Keller-Ramey J, White SM, Campeau PM, Gripp KW, Kutsche K (2019) Gain-of-function mutations in KCNN3 encoding the small-conductance Ca(2+)-activated K(+) channel SK3 cause Zimmermann-Laband syndrome. Am J Hum Genet 104:1139–1157. https://doi.org/10.1016/j.ajhg.2019.04.012
Baulac S, Gourfinkel-An I, Couarch P, Depienne C, Kaminska A, Dulac O, Baulac M, LeGuern E, Nabbout R (2008) A novel locus for generalized epilepsy with febrile seizures plus in French families. Arch Neurol 65:943–951. https://doi.org/10.1001/archneur.65.7.943
Beauregard-Lacroix E, Pacheco-Cuellar G, Ajeawung NF, Tardif J, Dieterich K, Dabir T, Vind-Kezunovic D, White SM, Zadori D, Castiglioni C, Tranebjaerg L, Torring PM, Blair E, Wisniewska M, Camurri MV, van Bever Y, Molidperee S, Taylor J, Dionne-Laporte A, Sisodiya SM, Hennekam RCM, Campeau PM (2020) DOORS syndrome and a recurrent truncating ATP6V1B2 variant. Genet Med. https://doi.org/10.1038/s41436-020-00950-9
Beauregard-Lacroix E, Pacheco-Cuellar G, Ajeawung NF, Tardif J, Dieterich K, Dabir T, Vind-Kezunovic D, White SM, Zadori D, Castiglioni C, Tranebjaerg L, Torring PM, Blair E, Wisniewska M, Camurri MV, van Bever Y, Molidperee S, Taylor J, Dionne-Laporte A, Sisodiya SM, Hennekam RCM, Campeau PM (2021) DOORS syndrome and a recurrent truncating ATP6V1B2 variant. Genet Med 23:149–154. https://doi.org/10.1038/s41436-020-00950-9
Beyenbach KW, Wieczorek H (2006) The V-type H+ ATPase: molecular structure and function, physiological roles and regulation. J Exp Biol 209:577–589. https://doi.org/10.1242/jeb.02014
Bodzeta A, Kahms M, Klingauf J (2017) The presynaptic v-ATPase reversibly disassembles and thereby modulates exocytosis but is not part of the fusion machinery. Cell Rep 20:1348–1359. https://doi.org/10.1016/j.celrep.2017.07.040
Breton S, Brown D (2013) Regulation of luminal acidification by the V-ATPase. Physiology (bethesda) 28:318–329. https://doi.org/10.1152/physiol.00007.2013
Brown D, Paunescu TG, Breton S, Marshansky V (2009) Regulation of the V-ATPase in kidney epithelial cells: dual role in acid-base homeostasis and vesicle trafficking. J Exp Biol 212:1762–1772. https://doi.org/10.1242/jeb.028803
Campeau PM, Hennekam RC (2014) DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome. Am J Med Genet C Semin Med Genet 166C:327–332. https://doi.org/10.1002/ajmg.c.31412
Campeau PM, Kasperaviciute D, Lu JT, Burrage LC, Kim C, Hori M, Powell BR, Stewart F, Felix TM, van den Ende J, Wisniewska M, Kayserili H, Rump P, Nampoothiri S, Aftimos S, Mey A, Nair LD, Begleiter ML, De Bie I, Meenakshi G, Murray ML, Repetto GM, Golabi M, Blair E, Male A, Giuliano F, Kariminejad A, Newman WG, Bhaskar SS, Dickerson JE, Kerr B, Banka S, Giltay JC, Wieczorek D, Tostevin A, Wiszniewska J, Cheung SW, Hennekam RC, Gibbs RA, Lee BH, Sisodiya SM (2014) The genetic basis of DOORS syndrome: an exome-sequencing study. Lancet Neurol 13:44–58. https://doi.org/10.1016/S1474-4422(13)70265-5
Cantwell RJ (1975) Congenital sensori-neural deafness associated with onycho-osteo dystrophy and mental retardation (D.O.O.R. syndrome). Humangenetik 26:261–265. https://doi.org/10.1007/BF00281463
Castori M, Valiante M, Pascolini G, Leuzzi V, Pizzuti A, Grammatico P (2013) Clinical and genetic study of two patients with Zimmermann-Laband syndrome and literature review. Eur J Med Genet 56:570–576. https://doi.org/10.1016/j.ejmg.2013.08.004
Castroflorio E, den Hoed J, Svistunova D, Finelli MJ, Cebrian-Serrano A, Corrochano S, Bassett AR, Davies B, Oliver PL (2021) The Ncoa7 locus regulates V-ATPase formation and function, neurodevelopment and behaviour. Cell Mol Life Sci 78:3503–3524. https://doi.org/10.1007/s00018-020-03721-6
Corbett MA, Bahlo M, Jolly L, Afawi Z, Gardner AE, Oliver KL, Tan S, Coffey A, Mulley JC, Dibbens LM, Simri W, Shalata A, Kivity S, Jackson GD, Berkovic SF, Gecz J (2010) A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24. Am J Hum Genet 87:371–375. https://doi.org/10.1016/j.ajhg.2010.08.001
Di Giovanni J, Boudkkazi S, Mochida S, Bialowas A, Samari N, Leveque C, Youssouf F, Brechet A, Iborra C, Maulet Y, Moutot N, Debanne D, Seagar M, El Far O (2010) V-ATPase membrane sector associates with synaptobrevin to modulate neurotransmitter release. Neuron 67:268–279. https://doi.org/10.1016/j.neuron.2010.06.024
Falace A, Filipello F, La Padula V, Vanni N, Madia F, De Pietri TD, de Falco FA, Striano P, Dagna Bricarelli F, Minetti C, Benfenati F, Fassio A, Zara F (2010) TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy. Am J Hum Genet 87:365–370. https://doi.org/10.1016/j.ajhg.2010.07.020
Falace A, Buhler E, Fadda M, Watrin F, Lippiello P, Pallesi-Pocachard E, Baldelli P, Benfenati F, Zara F, Represa A, Fassio A, Cardoso C (2014) TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway. Proc Natl Acad Sci USA 111:2337–2342. https://doi.org/10.1073/pnas.1316294111
Fernandes AC, Uytterhoeven V, Kuenen S, Wang YC, Slabbaert JR, Swerts J, Kasprowicz J, Aerts S, Verstreken P (2014) Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration. J Cell Biol 207:453–462. https://doi.org/10.1083/jcb.201406026
Finelli MJ, Oliver PL (2017) TLDc proteins: new players in the oxidative stress response and neurological disease. Mamm Genome 28:395–406. https://doi.org/10.1007/s00335-017-9706-7
Finelli MJ, Sanchez-Pulido L, Liu KX, Davies KE, Oliver PL (2016) The evolutionarily conserved Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) domain is neuroprotective against oxidative stress. J Biol Chem 291:2751–2763. https://doi.org/10.1074/jbc.M115.685222
Finelli MJ, Aprile D, Castroflorio E, Jeans A, Moschetta M, Chessum L, Degiacomi MT, Grasegger J, Lupien-Meilleur A, Bassett A, Rossignol E, Campeau PM, Bowl MR, Benfenati F, Fassio A, Oliver PL (2019) The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons. Hum Mol Genet 28:584–597. https://doi.org/10.1093/hmg/ddy370
Forgac M (2007) Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat Rev Mol Cell Biol 8:917–929. https://doi.org/10.1038/nrm2272
Fukai R, Saitsu H, Tsurusaki Y, Sakai Y, Haginoya K, Takahashi K, Hubshman MW, Okamoto N, Nakashima M, Tanaka F, Miyake N, Matsumoto N (2016) De novo KCNH1 mutations in four patients with syndromic developmental delay, hypotonia and seizures. J Hum Genet 61:381–387. https://doi.org/10.1038/jhg.2016.1
Gabbett MT, Clark RC, McGaughran JM (2008) A second case of severe mental retardation and absent nails of hallux and pollex (Temple-Baraitser syndrome). Am J Med Genet A 146A:450–452. https://doi.org/10.1002/ajmg.a.32129
Gao X, Dai P, Yuan YY (2021) Correspondence on “DOORS syndrome and a recurrent truncating ATP6V1B2 variant” by Beauregard-Lacroix et al. Genet Med. https://doi.org/10.1038/s41436-021-01167-0
Gomez-Varela D, Zwick-Wallasch E, Knotgen H, Sanchez A, Hettmann T, Ossipov D, Weseloh R, Contreras-Jurado C, Rothe M, Stuhmer W, Pardo LA (2007) Monoclonal antibody blockade of the human Eag1 potassium channel function exerts antitumor activity. Cancer Res 67:7343–7349. https://doi.org/10.1158/0008-5472.CAN-07-0107
Gonda X, Eszlari N, Anderson IM, Deakin JF, Bagdy G, Juhasz G (2016) Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression. Transl Psychiatry 6:e945. https://doi.org/10.1038/tp.2016.221
Goodman RM, Lockareff S, Gwinup G (1969) Hereditary congenital deafness with onychodystrophy. Arch Otolaryngol 90:474–477. https://doi.org/10.1001/archotol.1969.00770030476012
Grube S, Gerchen MF, Adamcio B, Pardo LA, Martin S, Malzahn D, Papiol S, Begemann M, Ribbe K, Friedrichs H, Radyushkin KA, Muller M, Benseler F, Riggert J, Falkai P, Bickeboller H, Nave KA, Brose N, Stuhmer W, Ehrenreich H (2011) A CAG repeat polymorphism of KCNN3 predicts SK3 channel function and cognitive performance in schizophrenia. EMBO Mol Med 3:309–319. https://doi.org/10.1002/emmm.201100135
Hurtado-Lorenzo A, Skinner M, El Annan J, Futai M, Sun-Wada GH, Bourgoin S, Casanova J, Wildeman A, Bechoua S, Ausiello DA, Brown D, Marshansky V (2006) V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nat Cell Biol 8:124–136. https://doi.org/10.1038/ncb1348
Inuzuka LM, Macedo-Souza LI, Della-Rippa B, Monteiro FP, Delgado DS, Godoy LF, Ramos L, de Athayde Costa LS, Garzon E, Kok F (2020) ATP6V1B2-related epileptic encephalopathy. Epileptic Disord 22:317–322. https://doi.org/10.1684/epd.2020.1166
James AW, Miranda SG, Culver K, Hall BD, Golabi M (2007) DOOR syndrome: clinical report, literature review and discussion of natural history. Am J Med Genet A 143A:2821–2831. https://doi.org/10.1002/ajmg.a.32054
Kondapalli KC, Prasad H, Rao R (2014) An inside job: how endosomal Na(+)/H(+) exchangers link to autism and neurological disease. Front Cell Neurosci 8:172. https://doi.org/10.3389/fncel.2014.00172
Kondoh T, Tsuru A, Matsumoto T, Matsuzaka T, Tsuji Y (1999) Autosomal dominant onychodystrophy and congenital sensorineural deafness. J Hum Genet 44:60–62. https://doi.org/10.1007/s100380050109
Kortum F, Caputo V, Bauer CK, Stella L, Ciolfi A, Alawi M, Bocchinfuso G, Flex E, Paolacci S, Dentici ML, Grammatico P, Korenke GC, Leuzzi V, Mowat D, Nair LD, Nguyen TT, Thierry P, White SM, Dallapiccola B, Pizzuti A, Campeau PM, Tartaglia M, Kutsche K (2015) Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome. Nat Genet 47:661–667. https://doi.org/10.1038/ng.3282
Krey JF, Dumont RA, Wilmarth PA, David LL, Johnson KR, Barr-Gillespie PG (2018) ELMOD1 stimulates ARF6-GTP hydrolysis to stabilize apical structures in developing vestibular hair cells. J Neurosci 38:843–857. https://doi.org/10.1523/JNEUROSCI.2658-17.2017
Laband PF, Habib G, Humphreys GS (1964) Hereditary Gingival Fibromatosis. Report of an Affected Family with Associated Splenomegaly and Skeletal and Soft-Tissue Abnormalities. Oral Surg Oral Med Oral Pathol 17:339–351. https://doi.org/10.1016/0030-4220(64)90506-7
Lin L, Lyu Q, Kwan PY, Zhao J, Fan R, Chai A, Lai CSW, Chan YS, Shen X, Lai KO (2020) The epilepsy and intellectual disability-associated protein TBC1D24 regulates the maintenance of excitatory synapses and animal behaviors. PLoS Genet 16:e1008587. https://doi.org/10.1371/journal.pgen.1008587
Matsuda S, Okada N, Kodama T, Honda T, Iida T (2012) A cytotoxic type III secretion effector of Vibrio parahaemolyticus targets vacuolar H+-ATPase subunit c and ruptures host cell lysosomes. PLoS Pathog 8:e1002803. https://doi.org/10.1371/journal.ppat.1002803
Megarbane A, Al-Ali R, Choucair N, Lek M, Wang E, Ladjimi M, Rose CM, Hobeika R, Macary Y, Temanni R, Jithesh PV, Chouchane A, Sastry KS, Thomas R, Tomei S, Liu W, Marincola FM, MacArthur D, Chouchane L (2016) Temple-baraitser syndrome and zimmermann-laband syndrome: one clinical entity? BMC Med Genet 17:42. https://doi.org/10.1186/s12881-016-0304-4
Menendez I, Carranza C, Herrera M, Marroquin N, Foster J 2nd, Cengiz FB, Bademci G, Tekin M (2017) Dominant deafness-onychodystrophy syndrome caused by an ATP6V1B2 mutation. Clin Case Rep 5:376–379. https://doi.org/10.1002/ccr3.761
Merkulova M, Paunescu TG, Azroyan A, Marshansky V, Breton S, Brown D (2015) Mapping the H(+) (V)-ATPase interactome: identification of proteins involved in trafficking, folding, assembly and phosphorylation. Sci Rep 5:14827. https://doi.org/10.1038/srep14827
Milh M, Falace A, Villeneuve N, Vanni N, Cacciagli P, Assereto S, Nabbout R, Benfenati F, Zara F, Chabrol B, Villard L, Fassio A (2013) Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy. Hum Mutat 34:869–872. https://doi.org/10.1002/humu.22318
Moghadam H, Statten P (1972) Hereditary sensorineural hearing loss associated with onychodystrophy and digital malformations. Can Med Assoc J 107:310–312
Morel N, Dedieu JC, Philippe JM (2003) Specific sorting of the a1 isoform of the V-H+ATPase a subunit to nerve terminals where it associates with both synaptic vesicles and the presynaptic plasma membrane. J Cell Sci 116:4751–4762. https://doi.org/10.1242/jcs.00791
Mucha BE, Banka S, Ajeawung NF, Molidperee S, Chen GG, Koenig MK, Adejumo RB, Till M, Harbord M, Perrier R, Lemyre E, Boucher RM, Skotko BG, Waxler JL, Thomas MA, Hodge JC, Gecz J, Nicholl J, McGregor L, Linden T, Sisodiya SM, Sanlaville D, Cheung SW, Ernst C, Campeau PM (2019) A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay. Genet Med 21:1058–1064. https://doi.org/10.1038/s41436-018-0290-3
Murata Y, Sun-Wada GH, Yoshimizu T, Yamamoto A, Wada Y, Futai M (2002) Differential localization of the vacuolar H+ pump with G subunit isoforms (G1 and G2) in mouse neurons. J Biol Chem 277:36296–36303. https://doi.org/10.1074/jbc.M200586200
Mutch SA, Kensel-Hammes P, Gadd JC, Fujimoto BS, Allen RW, Schiro PG, Lorenz RM, Kuyper CL, Kuo JS, Bajjalieh SM, Chiu DT (2011) Protein quantification at the single vesicle level reveals that a subset of synaptic vesicle proteins are trafficked with high precision. J Neurosci 31:1461–1470. https://doi.org/10.1523/JNEUROSCI.3805-10.2011
Nakamura N, Tanaka S, Teko Y, Mitsui K, Kanazawa H (2005) Four Na+/H+ exchanger isoforms are distributed to Golgi and post-Golgi compartments and are involved in organelle pH regulation. J Biol Chem 280:1561–1572. https://doi.org/10.1074/jbc.M410041200
Obara M, Szeliga M, Albrecht J (2008) Regulation of pH in the mammalian central nervous system under normal and pathological conditions: facts and hypotheses. Neurochem Int 52:905–919. https://doi.org/10.1016/j.neuint.2007.10.015
Oot RA, Couoh-Cardel S, Sharma S, Stam NJ, Wilkens S (2017) Breaking up and making up: the secret life of the vacuolar H(+)-ATPase. Protein Sci 26:896–909. https://doi.org/10.1002/pro.3147
Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, Toillon RA, Delcourt P, Prevarskaya N (2001) Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: possible involvement of a h-ether.a-gogo K+ channel. Recept Channels 7:345–356
Parzefall T, Frohne A, Koenighofer M, Neesen J, Laccone F, Eckl-Dorna J, Waters JJ, Schreiner M, Amr SS, Ashton E, Schoefer C, Gstoettner W, Frei K, Lucas T (2020) A novel variant in the TBC1D24 lipid-binding pocket causes autosomal dominant hearing loss: evidence for a genotype-phenotype correlation. Front Cell Neurosci 14:585669. https://doi.org/10.3389/fncel.2020.585669
Peng W, Casey AK, Fernandez J, Carpinone EM, Servage KA, Chen Z, Li Y, Tomchick DR, Starai VJ, Orth K (2020) A distinct inhibitory mechanism of the V-ATPase by Vibrio VopQ revealed by cryo-EM. Nat Struct Mol Biol 27:589–597. https://doi.org/10.1038/s41594-020-0429-1
Popp B, Ekici AB, Thiel CT, Hoyer J, Wiesener A, Kraus C, Reis A, Zweier C (2017) Exome Pool-Seq in neurodevelopmental disorders. Eur J Hum Genet 25:1364–1376. https://doi.org/10.1038/s41431-017-0022-1
Qazi QH, Nangia BS (1984) Abnormal distal phalanges and nails, deafness, mental retardation, and seizure disorder: a new familial syndrome. J Pediatr 104:391–394. https://doi.org/10.1016/s0022-3476(84)81101-4
Rajab A, Riaz A, Paul G, Al-Khusaibi S, Chalmers R, Patton MA (2000) Further delineation of the DOOR syndrome. Clin Dysmorphol 9:247–251. https://doi.org/10.1097/00019605-200009040-00003
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
Robinson GC, Miller JR, Bensimon JR (1962) Familial ectodermal dysplasia with sensori-neural deafness and other anomalies. Pediatrics 30:797–802
Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S, Kruger M, Stainier DY (2015) Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524:230–233. https://doi.org/10.1038/nature14580
Santos M, Reis-Rego A, Coutinho M, Almeida ESC (2019) DOOR syndrome: a case report and its embryological basis. Int J Pediatr Otorhinolaryngol 117:57–60. https://doi.org/10.1016/j.ijporl.2018.11.015
Sennoune SR, Martinez-Zaguilan R (2012) Vacuolar H(+)-ATPase signaling pathway in cancer. Curr Protein Pept Sci 13:152–163. https://doi.org/10.2174/138920312800493197
Shaw M, Winczewska-Wiktor A, Badura-Stronka M, Koirala S, Gardner A, Kuszel L, Kowal P, Steinborn B, Starczewska M, Garry S, Scheffer IE, Berkovic SF, Gecz J (2020) EXOME REPORT: Novel mutation in ATP6V1B2 segregating with autosomal dominant epilepsy, intellectual disability and mild gingival and nail abnormalities. Eur J Med Genet 63:103799. https://doi.org/10.1016/j.ejmg.2019.103799
Simons C, Rash LD, Crawford J, Ma L, Cristofori-Armstrong B, Miller D, Ru K, Baillie GJ, Alanay Y, Jacquinet A, Debray FG, Verloes A, Shen J, Yesil G, Guler S, Yuksel A, Cleary JG, Grimmond SM, McGaughran J, King GF, Gabbett MT, Taft RJ (2015) Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy. Nat Genet 47:73–77. https://doi.org/10.1038/ng.3153
Tagliatti E, Fadda M, Falace A, Benfenati F, Fassio A (2016) Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse. Elife. https://doi.org/10.7554/eLife.10116
Takahashi KI, Copenhagen DR (1996) Modulation of neuronal function by intracellular pH. Neurosci Res 24:109–116. https://doi.org/10.1016/0168-0102(95)00989-2
Takamori S, Holt M, Stenius K, Lemke EA, Gronborg M, Riedel D, Urlaub H, Schenck S, Brugger B, Ringler P, Muller SA, Rammner B, Grater F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmuller H, Heuser J, Wieland F, Jahn R (2006) Molecular anatomy of a trafficking organelle. Cell 127:831–846. https://doi.org/10.1016/j.cell.2006.10.030
Temple IK, Baraitser M (1991) Severe mental retardation and absent nails of hallux and pollex. Am J Med Genet 41:173–175. https://doi.org/10.1002/ajmg.1320410207
Tinker RJ, Burghel GJ, Garg S, Steggall M, Cuvertino S, Banka S (2020) Haploinsufficiency of ATP6V0C possibly underlies 16p13.3 deletions that cause microcephaly, seizures, and neurodevelopmental disorder. Am J Med Genet A. https://doi.org/10.1002/ajmg.a.61905
Tona R, Chen W, Nakano Y, Reyes LD, Petralia RS, Wang YX, Starost MF, Wafa TT, Morell RJ, Cravedi KD, du Hoffmann J, Miyoshi T, Munasinghe JP, Fitzgerald TS, Chudasama Y, Omori K, Pierpaoli C, Banfi B, Dong L, Belyantseva IA, Friedman TB (2019) The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy. Hum Mol Genet 28:1530–1547. https://doi.org/10.1093/hmg/ddy445
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
Ufartes R, Schneider T, Mortensen LS, de Juan RC, Hentrich K, Knoetgen H, Beilinson V, Moebius W, Tarabykin V, Alves F, Pardo LA, Rawlins JN, Stuehmer W (2013) Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice. Hum Mol Genet 22:2247–2262. https://doi.org/10.1093/hmg/ddt076
Urrego D, Tomczak AP, Zahed F, Stuhmer W, Pardo LA (2014) Potassium channels in cell cycle and cell proliferation. Philos Trans R Soc Lond B Biol Sci 369:20130094. https://doi.org/10.1098/rstb.2013.0094
Walbaum R, Fontaine G, Lienhardt J, Piquet JJ (1970) [Familial deafness with osteo-onycho-dysplasia]. J Genet Hum 18:101–108
Wang F, Gatica D, Ying ZX, Peterson LF, Kim P, Bernard D, Saiya-Cork K, Wang S, Kaminski MS, Chang AE, Phillips T, Klionsky DJ, Malek SN (2019) Follicular lymphoma-associated mutations in vacuolar ATPase ATP6V1B2 activate autophagic flux and mTOR. J Clin Invest 129:1626–1640. https://doi.org/10.1172/JCI98288
White SM, Fahey M (2011) Report of a further family with dominant deafness-onychodystrophy (DDOD) syndrome. Am J Med Genet A 155A:2512–2515. https://doi.org/10.1002/ajmg.a.34184
Woody SK, Zhou H, Ibrahimi S, Dong Y, Zhao L (2016) Human ApoE varepsilon2 promotes regulatory mechanisms of bioenergetic and synaptic function in female brain: a focus on V-type H+-ATPase. J Alzheimers Dis 53:1015–1031. https://doi.org/10.3233/JAD-160307
Yuan Y, Zhang J, Chang Q, Zeng J, Xin F, Wang J, Zhu Q, Wu J, Lu J, Guo W, Yan X, Jiang H, Zhou B, Li Q, Gao X, Yuan H, Yang S, Han D, Mao Z, Chen P, Lin X, Dai P (2014) De novo mutation in ATP6V1B2 impairs lysosome acidification and causes dominant deafness-onychodystrophy syndrome. Cell Res 24:1370–1373. https://doi.org/10.1038/cr.2014.77
Zadori D, Szalardy L, Reisz Z, Kovacs GG, Maszlag-Torok R, Ajeawung NF, Vecsei L, Campeau PM, Klivenyi P (2020) Clinicopathological relationships in an aged case of DOORS syndrome with a p.Arg506X mutation in the ATP6V1B2 gene. Front Neurol 11:767. https://doi.org/10.3389/fneur.2020.00767
Zhang J, Chan YC, Ho JC, Siu CW, Lian Q, Tse HF (2012) Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-a-go-go 1 (hEAG1) potassium channel. Am J Physiol Cell Physiol 303:C115–C125. https://doi.org/10.1152/ajpcell.00326.2011
Zhang L, Hu L, Chai Y, Pang X, Yang T, Wu H (2014) A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable cause for nonsyndromic hearing impairment. Hum Mutat 35:814–818. https://doi.org/10.1002/humu.22558
Zhao H, Carney KE, Falgoust L, Pan JW, Sun D, Zhang Z (2016) Emerging roles of Na(+)/H(+) exchangers in epilepsy and developmental brain disorders. Prog Neurobiol 138–140:19–35. https://doi.org/10.1016/j.pneurobio.2016.02.002
Zhao W, Gao X, Qiu S, Gao B, Gao S, Zhang X, Kang D, Han W, Dai P, Yuan Y (2019) A subunit of V-ATPases, ATP6V1B2, underlies the pathology of intellectual disability. EBioMedicine 45:408–421. https://doi.org/10.1016/j.ebiom.2019.06.035
Zimmermann (1928) Uber anomalien des ektoderms. Vjschr Zahn-heilkd 44:419–434
Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM (2011) mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 334:678–683. https://doi.org/10.1126/science.1207056
Acknowledgements
Our research is supported by the grants from National key R&D project (2016YFC1000706, 2016YFC1000704), National Natural Science Foundation of China (81730029, 81873704, 81570929 and 61827805), Beijing Natural Science Foundation (7191011, 7192234), and Fostering Funds of Chinese PLA General Hospital for National Distinguished Young Scholar Science Fund (2017–JQPY–001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We apologize to colleagues whose work could not be cited due to limitations in the number of citations.
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Gao, X., Dai, P. & Yuan, YY. Genetic architecture and phenotypic landscape of deafness and onychodystrophy syndromes. Hum Genet 141, 821–838 (2022). https://doi.org/10.1007/s00439-021-02310-2
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DOI: https://doi.org/10.1007/s00439-021-02310-2