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Shifting the Focus of Molecular Syndromology from Individual Diagnoses to Outcome Analyses. Mol. Syndromol. (IF 1.1) Pub Date : 2023-07-18
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Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and/or Palate in the Netherlands. Mol. Syndromol. (IF 1.1) Pub Date : 2023-06-08 Lisca Florence Wurfbain,Inge Lucia Cox,Maria Francisca van Dooren,Augusta Maria Antonia Lachmeijer,Virginie Johanna Maria Verhoeven,Johanna Maria van Hagen,Malou Heijligers,Jolien Sietske Klein Wassink-Ruiter,Saskia Koene,Saskia Mariska Maas,Hermine Elisabeth Veenstra-Knol,Johannes Kristian Ploos van Amstel,Maarten Pieter Gerrit Massink,Aebele Barber Mink van der Molen,Marie-José Henriette van den
Objectives Clefts of the lip, alveolus and/or palate (CLA/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic/genetic
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Extensive, 3.8 Mb-Sized Deletion of 22q12 in a Patient with Bilateral Schwannoma, Intellectual Disability, Sensorineural Hearing Loss, and Epilepsy. Mol. Syndromol. (IF 1.1) Pub Date : 2023-06-02 Jakub Trizuljak,Jakub Duben,Ivona Blaháková,Zuzana Vrzalová,Kateřina Staňo Kozubík,Jiří Štika,Lenka Radová,Veronika Bergerová,Soňa Mejstříková,Věra Hořínová,Radim Jančálek,Šárka Pospíšilová,Michael Doubek
Introduction In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition
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Clinical Heterogeneity in Patients with Long QT Syndrome and Segregation of Single Nucleotide Variants and Clinical Symptoms in 17 Affected Families. Mol. Syndromol. (IF 1.1) Pub Date : 2023-06-02 Elcin Bora,Ayca Yıldız Bulut,Tufan Cankaya,Tayfun Cinleti,Halise Zeynep Genç,Emin Evren Ozcan,Ebru Ozpelit,Ayfer Ulgenalp,Ahmet Okay Caglayan
Introduction Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization characterized by a prolonged QT interval on the electrocardiogram. It increases the risk of ventricular arrhythmias, which can cause syncope or sudden cardiac death. In this study, we study the genotype-phenotype relationships of patients referred to us with suspected arrhythmia syndrome. Methods Seventeen cases
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VAMP2 Gene-Related Neurodevelopmental Disorder: A Differential Diagnosis for Rett/Angelman-Type Spectrum of Disorders. Mol. Syndromol. (IF 1.1) Pub Date : 2023-06-01 Danielle Bogue,Gavin Ryan,Evangeline Wassmer,Genomics England Research Consortium,Swati Naik
Introduction VAMP2 is an instrumental protein in neuronal synaptic transmission in the brain, facilitating neurotransmitter release. It is encoded by the VAMP2 gene, and pathogenic variants in this gene cause neurodevelopmental features including early onset axial hypotonia, intellectual disability, and features of autism spectrum disorder. To date, only three types of allelic variants (loss of function
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Reanalysis of Chromosomal Microarray Data Using a Smaller Copy Number Variant Call Threshold Identifies Four Cases with Heterozygous Multiexon Deletions of ARID1B, EHMT1, and FOXP1 Genes. Mol. Syndromol. (IF 1.1) Pub Date : 2023-05-23 Noriko Kubota,Ryojun Takeda,Jun Kobayashi,Eiko Hidaka,Eriko Nishi,Kyoko Takano,Keiko Wakui
Introduction Chromosomal microarray (CMA) is a highly accurate and established method for detecting copy number variations (CNVs) in clinical genetic testing. CNVs are important etiological factors for disorders such as intellectual disability, developmental delay, and multiple congenital anomalies. Recently developed analytical methods have facilitated the identification of smaller CNVs. Therefore
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Novel SYNGAP1 Variant in an Adult Individual Affected by Intellectual Disability and Epilepsy: A Cold Case Solved through Whole-Exome Sequencing. Mol. Syndromol. (IF 1.1) Pub Date : 2023-05-09 Giulia Rosti,Silvia Boeri,Maria Teresa Divizia,Livia Pisciotta,Maria Margherita Mancardi,Margherita Lerone,Maria Cerminara,Martina Servetti,Giovanni Spirito,Diego Vozzi,Marco Fontana,Stefano Gustincich,Lino Nobili,Federico Zara,Aldamaria Puliti
Introduction Nowadays, whole-exome sequencing (WES) analysis is an essential part in the diagnostic pathway of individuals with complex phenotypes when routine exams, such as array-CGH and gene panels, have proved inconclusive. However, data on the diagnostic rate of WES analysis in adult individuals, negative to first-tier tests, are lacking. This is because initiatives with the aim of diagnosing
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Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach. Mol. Syndromol. (IF 1.1) Pub Date : 2023-05-05 Emna Bouatrous,Sonia Nouira,Samia Menif,Houyem Ouragini
Introduction NADH-cytochrome b5 reductase deficiency due to pathogenic variants in the CYB5R3 gene causes recessive congenital methemoglobinemia (RCM) type I or type II. In type I, cyanosis from birth is the only major symptom, and the enzyme deficiency is restricted only to erythrocytes. Whereas in type II, cyanosis is associated with severe neurological manifestations, and the enzyme deficiency is
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Co-Occurrence of Pallister-Killian Syndrome and Burkitt Lymphoma in a Patient with Near-Normal Neurocognitive Development. Mol. Syndromol. (IF 1.1) Pub Date : 2023-05-05 Kosuke Izumi,Rebecca D Ganetzky,Gerald B W Wertheim,Cara M Skraban,Emma C Bedoukian,Alisha Wilkens,Christopher Fincher,Nina H Thomas,Jill P Ginsberg,Susan R Rheingold,Laura K Conlin,Matthew A Deardorff
Background Pallister-Killian syndrome (PKS) is typically recognized by its features that include developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p. Case Presentation Here, we report a patient with PKS who was subsequently diagnosed with Burkitt lymphoma. Following the successful treatment of lymphoma
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Autism Spectrum Disorder in Two Unrelated Patients with Homozygous Variants in Either ALG8 or ALG11 Mol. Syndromol. (IF 1.1) Pub Date : 2023-04-21 Gozde Uzunyayla-Inci, Ertugrul Kiykim, Tanyel Zubarioglu, Gözde Yeşil, CIGDEM AKTUGLU ZEYBEK
Background: Autism spectrum disorder (ASD) is used to describe individuals with a specific combination of disorders in social communication and repetitive behaviors, highly restricted interests, and/or sensory behavior that begin early in life. The prevalence of ASD has been increasing rapidly in recent years. Pathophysiology of ASDs remains still unclear; however, genetic defects and multifactorial
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Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile Mol. Syndromol. (IF 1.1) Pub Date : 2023-04-19 José Miguel Cárdenas, Diane Vergara, Scarlet Witting, Fernanda Balut, Patricio Guerra, José Tomás Mesa, Sebastián Silva, Javiera Tello, Alvaro Retamales, Andrés Barrios, Fernando Pinto, Víctor Faundes, Mónica Troncoso
Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared
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Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes Mol. Syndromol. (IF 1.1) Pub Date : 2023-04-12 Mara Grassi, Bernard Laubscher, Amit V. Pandey, Sibylle Tschumi, Franziska Graber, André Schaller, Marco Janner, Daniel Aeberli, Ekkehard Hewer, Jean-Marc Nuoffer, Matthias Gautschi
Introduction: The p.(Arg85Trp) variant-specific phenotype of hepatocyte nuclear factor 4 alpha shows a complex clinical picture affecting three different organ systems and their corresponding metabolisms. Little is known about the molecular mechanisms involved and their relationship with the diverse symptoms seen in the context of this specific variant. Here, we present data of a new patient that expand
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Identification of a Novel de novo Splicing Mutation in Duchenne Muscular Dystrophy Gene in an Iranian Family Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-31 Saeideh Kavousi, Azam Pourahmadiyan, Fatemeh Soleymani, Mehrdad Noruzinia
Introduction: Duchenne muscular dystrophy (DMD) (NM_004006.3) is one of the most notable neuromuscular disorders of early years. The majority of DMD cases are caused by deletions or duplications in dystrophin, while point mutations are less prevalent in dystrophin abnormalities. It is a common knowledge that the severity of the disease depends on the effect of the mutation on the translational reading
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Description of Phenotypic Heterogeneity in a GJC2-Related Family and Literature Review Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-30 Aida Ghasemi, Ali Reza Tavasoli, Mana Khojasteh, Mohammad Rohani, Afagh Alavi
Introduction: Homozygous and compound heterozygous variants in GJC2, the gene encoding connexin-47 protein, cause Pelizaeus-Merzbacher-like disease type 1 or hypomyelinating leukodystrophy 2 (HLD2), a severe infantile-onset hypomyelinating leukodystrophy, and rarely some milder phenotypes like hereditary spastic paraplegia (HSP) type 44 (SPG44) and subclinical leukodystrophy. Herein, we report an Iranian
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A Missense Pathogenic Variant in a Conserved Region of CNTNAP2 Is Associated with Obesity, Seizures, and Language Impairment in a Pakistani Family Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-30 Sara Naudhani, Adeel Ahmad, Fariya Khan Bazai, Muhammad Tariq Pervez, Azqa Zafar, Sajjad Ali Shah, Nafeesa Raheem, Abdul Hameed Baloch, Muhammad Mushtaq, Shakeela Daud
Introduction: In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood. Methods: By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T#x3e;A [p.Ile1124Asn]) in exon 20 of the CNTNAP2
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Recurrent Mutation (p.Arg718Pro) in the COMP Gene with Clinical Heterogeneity of Pseudoachondroplasia Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-29 Jaime Toral López, Luz María González Huerta
Introduction: Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are allelic and caused by mutations in the COMP gene. Other mutations in the genes MMP13, AIFM1, B3GALT6, MATN3, COL9A1, COL9A2, COL9A3, and SLC26A2 have also been associated with evidence of dysplasia in the epiphysis, metaphysis, and spine. Case Presentation: We report on the first Mexican patient diagnosed with PSACH
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X-Linked Hydrocephalus with New L1CAM Pathogenic Variants: Review of the Most Prevalent Molecular and Phenotypic Features Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-28 Rania R. Ahmed, Amina M. Medhat, Germine M. Hamdy, Laila K.E. Effat, Mohamed S. Abdel-Hamid, Ghada M.H. Abdel-Salam
Introduction: The underlying molecular defects of congenital hydrocephalus are heterogeneous and many isolated forms of hydrocephalus remain unsolved at the molecular level. Congenital hydrocephalus in males associated with agenesis of the corpus callosum is a notable characteristic of L1CAM gene which is by far the most common genetic etiology of congenital hydrocephalus. Methods and Results: Sequencing
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Clinical and Genetic Characteristics of Patients with Unexplained Intellectual Disability/Developmental Delay without Epilepsy Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-14 Hamide Betul Gerik-Celebi, Hilal Aydin, Hilmi Bolat, Gul Unsel-Bolat
Introduction: Global developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) are mainly evaluated under the neurodevelopmental disorder framework. In this study, we aimed to determine the genetic diagnosis yield using step-by-step genetic analysis in 38 patients with unexplained ID/DD and/or ASD. Methods: In 38 cases (27 male, 11 female) with unexplained ID/DD and/or
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DPAGT1-CDG: Report of Two New Pediatric Patients and Brief Review of the Literature Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-08 Özlem Özsoy, Tayfun Cinleti, Çağatay Günay, Gamze Sarıkaya Uzan, Mehmet Can Yeşilmen, Hanns Lochmüller, Rita Horvath, Uluç Yiş, Yavuz Oktay, Semra Hiz Kurul
Introduction: Congenital glycosylation disorders are multisystem diseases with heterogeneous clinical manifestations caused by defects in the synthesis of the glycan moiety of glycoproteins or glycolipids or the binding of glycans to proteins and lipids. DPAGT1 (UDP-GlcNAc: dolichol phosphate N-acetylglucosamine-1-phosphotransferase) is an initiating protein in the biosynthetic pathway of dolichol-linked
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Pure Interstitial Trisomy 11q Arising from a Nonrecurrent 11q13.1q22.3 Mosaic Intrachromosomal Duplication in a Patient with Craniofacial Dysmorphism and Genital Anomalies Mol. Syndromol. (IF 1.1) Pub Date : 2023-03-01 Daniel Martínez Anaya, María del Rocío Juárez-Velázquez, Sinuhé Reyes Ruvalcaba, María del Pilar Navarrete-Meneses, Consuelo Salas Labadía, Esther Lieberman Hernández, Patricia Pérez-Vera
Introduction: The pure interstitial trisomy 11q11q23.2 is an uncommon genomic disorder associated with nonrecurrent intrachromosomal duplications. The phenotype is characterized by intellectual disability and craniofacial abnormalities. Given their uncommonness, a comprehensive genotype-phenotype correlation has not fully been defined. Case Presentation: We report the clinical and cytogenomic characterization
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Mutated Transcripts of ZEB2 Do Not Undergo Nonsense-Mediated Decay in Mowat-Wilson Syndrome Mol. Syndromol. (IF 1.1) Pub Date : 2023-02-20 Naz Güleray Lafcı, Beren Karaosmanoglu, Ekim Z. Taskiran, Pelin Ozlem Simsek-Kiper, Gülen Eda Utine
Introduction: Mowat-Wilson syndrome (MWS) is an autosomal-dominant complex developmental disorder characterized by distinctive facial appearance, intellectual disability, epilepsy, and various clinically heterogeneous abnormalities reminiscent of neurocristopathies. MWS is caused by haploinsufficiency of ZEB2 due to heterozygous point mutations and copy number variations. Case Presentation: We report
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Differential Diagnosis of Pulmonary Veno-Occlusive Disease and/or Pulmonary Capillary Hemangiomatosis after Identification of Two Novel EIF2AK4 Variants by Whole-Exome Sequencing Mol. Syndromol. (IF 1.1) Pub Date : 2023-02-01 Jong Eun Park, Sung-A Chang, Shin Yi Jang, Kyung Soo Lee, Duk-Kyung Kim, Chang-Seok Ki
Background: Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. Pulmonary arterial hypertension (PAH) and PVOD/PCH are clinically similar, but there is a risk of drug-induced pulmonary edema when PCH patients receive the PAH therapy. Therefore, early diagnosis of PVOD/PCH is important. Objectives: We report the first case
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Dicentric Recombinant Chromosome 18 due to Maternal Paracentric Inversion Analyzed by Array CGH Mol. Syndromol. (IF 1.1) Pub Date : 2023-02-01 Özlem Anlaş, Akgün Ölmez, Birsen Karaman, Füsun Düzcan, Selçuk Yüksel, Funda Tümkaya, Gülseren Bağcı, Cavidan Nur Semerci Gündüz
Introduction: Chromosomal abnormalities are mostly found in 0.5–0.8% of live-born infants with developmental and morphological defects. Paracentric inversions are structural intrachromosomal rearrangements resulting in a risk of chromosomally unbalanced gametes in carriers. Case Presentation: Herein, we report a patient with dicentric rearrangement of chromosome 18 due to maternal paracentric inversion
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Identification of a Novel Nonsense Variant in the DLL3 Gene Underlying Spondylocostal Dysostosis in a Consanguineous Pakistani Family Mol. Syndromol. (IF 1.1) Pub Date : 2023-02-01 Feroz Khan, Abida Arshad, Asmat Ullah, Ellen Steenackers, Geert Mortier, Wasim Ahmad, Muhammad Arshad, Sarmir Khan, Amir Hayat, Ikram Khan, Muhammad Asim Khan, Wim Van Hul
Introduction: Spondylocostal dysostosis (SCD) is characterized by multiple vertebral abnormalities associated with abnormalities of the ribs. Five genes causative for the disease have been identified. These include DLL3 (OMIM *602768), MESP2 (OMIM #608681), LFNG (OMIM #609813), TBX6 (OMIM *602427), and HES7 (OMIM *608059). Methods: In the current study, we investigated a Pakistani consanguineous family
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Sequence Variants in MEGF8 and GJA1 Underlying Syndactyly Mol. Syndromol. (IF 1.1) Pub Date : 2023-02-01
Introduction: Syndactyly is a common congenital limb malformation. It occurs due to embryological failure of digit separation during limb development. Syndactyly often runs in families with an incidence of about one out of every 2,500–3,000 live births. Methods: Here, we have reported two families presenting features of severe forms of syndactyly. The disorder segregated in autosomal recessive in one
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The New Youngest Case of Grange Syndrome with a Novel Biallelic Pathogenic Variant in YY1AP1 Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-26 Taner Karakaya, Ayberk Turkyilmaz, Deniz Eris, Mehtap Kaya, Kupra Oksuz, Meltem Aygul Eryigit, Gizem Gönen
Introduction: Grange syndrome (OMIM 602531) is characterized by a constellation of symptoms of hypertension, stenosis, or occlusion of different arteries (including the cerebral, renal, abdominal, and coronary vessels) with a variable occurrence of brachysyndactyly, bone fragility, and congenital heart defects. Learning disabilities were also reported in some cases. Biallelic pathogenic variants in
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Triosephosphate Isomerase Deficiency: E105D Mutation in Unrelated Patients and Review of the Literature Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-19 Arzu Selamioğlu, Meryem Karaca, Mehmet Cihan Balcı, Hüseyin Kutay Körbeyli, Aslı Durmuş, Edibe Pembegül Yıldız, Serap Karaman, Gülden Fatma Gökçay
Introduction: Chronic haemolytic anaemia, increased susceptibility to infections, cardiomyopathy, neurodegeneration, and death in early childhood are the clinical findings of triosephosphate isomerase (TPI) deficiency, which is an ultra-rare disorder. The clinical and laboratory findings and the outcomes of 2 patients with TPI deficiency are reported, with a review of cases reported in the literature
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Report on a Case with Moreno-Nishimura-Schmidt Overgrowth Syndrome: A Clinically Delineated Disease Yet of an Unknown Origin! Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-17 Cybel Mehawej, Eliane Chouery, Ghada Al Hage Chehade, Yosra Bejaoui, Daniel Mahfoud, Maya Gerges, Valérie Delague, Nady El Hajj, Andre Megarbane
Introduction: Overgrowth syndromes are a heterogeneous group of genetic disorders characterized by excessive growth, often accompanied by additional clinical features, such as facial dysmorphism, hormonal imbalances, cognitive impairment, and increased risk for neoplasia. Moreno-Nishimura-Schmidt (M-N-S) overgrowth syndrome is a very rare overgrowth syndrome characterized by severe pre- and postnatal
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A Genetics Study in the Foreskin of Boys with Hypospadias Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-16 Irem Inanc, Dincer Avlan, Damla Eker, Hakan Gurkan
Introduction: Hypospadias is a malformation of the genitourinary system in males, characterized by the placement of the urethral opening in the ventral surface of the penis. Although controversies continue about etiology, endocrine disrupting chemicals that disrupt normal endocrine signaling at the receptor or signal transduction level are thought to play an essential role in etiology. This study aimed
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The First Congenital Disorders of Glycosylation Patient (Fetus) with Homozygous COG5 c.95T>G Variant Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-13 Murat Buyukdogan, Veysel Sabri Hancer, Ayhan Sucak
Introduction: Congenital disorders of glycosylation (CDG) are autosomal recessive hereditary genetic disorders characterized by abnormal glycosylation of N-linked oligosaccharides. Case Presentation: In this research, prenatal testing (24th week of pregnancy) revealed findings like polyhydramnios, hydrocephaly, abnormal facial features/shape, brain morphology abnormality, spina bifida, vertebral column
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Two Patients Diagnosed as Succinate Dehydrogenase Deficiency: Case Report Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-13 Burcu Civelek Ürey, Ahmet Cevdet Ceylan, Büşranur Çavdarlı, Ayşegül Neşe Çıtak Kurt, Oya Kıreker Köylü, Burak Yürek, Çiğdem Seher Kasapkara
Introductıon: Succinate dehydrogenase deficiency, also known as mitochondrial complex II deficiency, is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial disease. Mutations in the four genes SDHA, B, C,and D have been reported resulting in diverse clinical presentations. The vast majority of clinically affected individuals reported in the literature harbor genetic
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A Second Family with Myhre Syndrome Caused by the Same Recurrent SMAD4 Pathogenic Variation (p.Arg496Cys) Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-13 Şenol Demir, Ceren Alavanda, Gözde Yeşil, Ayça Dilruba Aslanger, Esra Arslan Ateş
Introduction: Myhre syndrome (MS; OMIM #139210) is a rare connective tissue disorder presenting with cardiovascular, respiratory, gastrointestinal, and skeletal system findings. Fewer than 100 patients were reported until recently, and all molecularly confirmed cases had de novo heterozygous gain-of-function mutations in the SMAD4 gene. Dysregulation of the TGF-beta signaling pathway leads to axial
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Identification of a Novel IQCE Large Deletion through Copy Number Variant Analysis from Whole-Exome Sequencing Data of a Patient with Postaxial Polydactyly Type A7 Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-13 Faidon-Nikolaos Tilemis, Nikolaos M. Marinakis, Konstantina Kosma, Florentia Fostira, Joanne Traeger-Synodinos
Introduction: Non-syndromic polydactyly has been associated with pathogenic variants in 11 genes until today, including IQCE gene. More precisely, loss-of-function of IQCE is associated with the autosomal recessive disorder postaxial polydactyly type A7 (PAPA7, MIM #617642). Case Presentation: A 3-year-old female patient was referred to our genetics department with postaxial polydactyly, syndactyly
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Case Report of Two Siblings Diagnosed with Osteogenesis Imperfecta Type XV with a New Mutation in the WNT1 Gene and Review of the Literature Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-11 Büşra Eser Çavdartepe, Rojan İpek
Introduction: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fractures and low bone mass. Recently, mutations of the WNT1 gene have been reported to be causative in OI. The mutation in WNT1 causes autosomal-recessive OI due to its critical role in bone formation. WNT1 mutations cause varying degrees of clinical severity, ranging from moderate to progressively deforming forms
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Acknowledgement to Reviewers Mol. Syndromol. (IF 1.1) Pub Date : 2023-01-04
Mol Syndromol 2022;13:551–551
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Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome Mol. Syndromol. (IF 1.1) Pub Date : 2022-12-23 G. Tutku Turgut, Ibrahim Halil Kalelioglu, Volkan Karaman, Tugba Sarac Sivrikoz, Birsen Karaman, Zehra Oya Uyguner, Tugba Kalayci
Introduction: GDF5-BMPR1B signaling pathway-associated chondrodysplasias are a genetically heterogeneous group of conditions with significant phenotypic and genotypic overlap, consisting of Hunter-Thompson-type acromesomelic dysplasia, Grebe dysplasia, and Du Pan syndrome. Constituting a spectrum of clinical severity, these disorders are characterized by disproportionate short stature mainly involving
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Novel Variant in the USP9X Gene Is Associated with Congenital Heart Disease in a Male Patient: A Case Report and Literature Review Mol. Syndromol. (IF 1.1) Pub Date : 2022-12-23 Cristiana Agazzi, Monia Magliozzi, Onofrio Iacoviello, Stefano Palladino, Maurizio Delvecchio, Maristella Masciopinto, Alessio Galati, Antonio Novelli, Francesco Andrea Causio, Giuseppe Zampino, Claudia Ruggiero, Rita Fischetto
Introduction: The X-chromosomal USP9X gene encodes a deubiquitylating enzyme involved in protein turnover and TGF-β signaling during fetal and neuronal development. USP9X variants in females are primarily associated with complete loss-of-function (LOF) alleles, leading to neurodevelopmental delay and intellectual disability, as well as a wide range of congenital anomalies. In contrast, USP9X missense
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First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations Mol. Syndromol. (IF 1.1) Pub Date : 2022-12-16 Jorge Román Corona-Rivera, Juan Carlos Zenteno, Leopoldo Gildardo López-Pérez, Emiy Yokoyama-Rebollar, Camilo E. Villarroel, Tania Barragán-Arévalo, Luis Ángel Montes-Almanza, Luz Consuelo Zepeda-Romero, Guadalupe Elena Morales-Domínguez, Christian Peña-Padilla, Lucina Bobadilla-Morales, Alfredo Corona-Rivera
Introduction: PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem
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Innovating Therapies for Down Syndrome: An International Virtual Conference of the T21 Research Society Mol. Syndromol. (IF 1.1) Pub Date : 2022-11-11 Eric D. Hamlett, Lisi Flores-Aguilar, Benjamin Handen, Marie-Claude Potier, Ann-Charlotte Granholm, Stephanie Sherman, Victoria Puig, Jonathan D. Santoro, María Carmona-Iragui, Anne-Sophie Rebillat, Elizabeth Head, André Strydom, Jorge Busciglio
Research focused on Down syndrome continued to gain momentum in the last several years and is advancing our understanding of how trisomy 21 (T21) modifies molecular and cellular processes. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. During the COVID pandemic, T21RS held its first virtual conference program, sponsored
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A Rare Contiguous Gene Deletion Leading to Trichothiodystrophy Type 4 and Glutaric Aciduria Type 3 Mol. Syndromol. (IF 1.1) Pub Date : 2022-11-10 Engin Demir, Neslihan Doğulu, Ceyda Tuna Kırsaçlıoğlu, Vehap Topçu, Fatma Tuba Eminoglu, Zarife Kuloğlu, Aydan Kansu
Introduction: Trichothiodystrophy type 4 and glutaric aciduria type 3 are rare autosomal recessive disorders caused by biallelic variants in the MPLKIP and SUGCT genes on chromosome 7p14, respectively. Trichothiodystrophy type 4 is characterized by neurologic and cutaneous abnormalities. Glutaric aciduria type 3 is a rare metabolic disorder with inconsistent phenotype and elevated urinary excretion
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Homozygous Val6Gly Variation in PRDM5 Gene Causing Brittle Cornea Syndrome: A New Turkish Case Mol. Syndromol. (IF 1.1) Pub Date : 2022-11-07 Aslıhan Sanrı, Selma Demir, Hakan Gurkan
Introduction: Brittle cornea syndrome (BCS) is a rare connective tissue disorder with ocular and systemic features. Extreme corneal thinning and fragility are the main hallmarks of BCS. Case Report: A 4-year-old boy presented with recurrent spontaneous corneal perforation. He had blue sclera, corneal leucoma, irregular iris, shallow anterior chamber, corneal astigmatism, and bilateral corneal thinning
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Expanded Phenotypic Spectrum or Multiple Syndromes? Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-28 Martin Poot
Mol Syndromol
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Overlapping Interstitial Deletions of the Region 9q22.33 to 9q33.3 of Three Patients Allow Pinpointing Candidate Genes for Epilepsy and Cleft Lip and Palate Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-27 Renata Szalai, Agnes Till, Andras Szabo, Bela Melegh, Kinga Hadzsiev, Marta Czako
Introduction: Patients carrying interstitial deletions of the long arm of chromosome 9 show similar features. These phenotypes are often characterized by developmental delay, intellectual disability, short stature, and dysmorphism. Previously reported deletions differ in size and location spanning from 9q21 to 9q34 and were mostly detected by conventional cytogenetic techniques. Methods: Based on clinical
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A Case of Short Stature Caused by a Mutation in the ACAN Gene Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-21 Emine Karatas, Mikail Demir, Firat Ozcelik, Leyla Kara, Esra Akyurek, Ugur Berber, Nihal Hatipoglu, Yusuf Ozkul, Munis Dundar
Introduction: Aggrecanopathies are rare disorders associated with idiopathic short stature. They are caused by pathogenic changes in the ACAN gene located on chromosome 15q26. In this study, we present a case of short stature caused by mutations in the ACAN gene. Case Presentation: A 3-year-3-month-old male patient was referred to us because of his short stature. Physical examination revealed proportional
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Severe Antenatal Hypertrophic Cardiomyopathy Secondary to ACAD9-Related Mitochondrial Complex I Deficiency Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-21 Charlotte Dubucs, Jacqueline Aziza, Agnès Sartor, François Heitz, Annick Sevely, Damien Sternberg, Claude Jardel, Tiscar Cavallé-Garrido, Steffen Albrecht, Chantal Bernard, Isabelle De Bie, Nicolas Chassaing
Introduction: Antenatal presentation of hypertrophic cardiomyopathy (HCM) is rare. We describe familial recurrence of antenatal HCM associated with intrauterine growth restriction and the diagnostic process undertaken. Methods: Two pregnancies with antenatal HCM were followed up. Biological assessment including metabolic analyses, genetic analyses, and respiratory chain study was performed. We describe
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A Novel Mutation in Melanocortin Receptor 2 and a Reported Mutation in Melanocortin Receptor 2 Accessory Protein: Three Chinese Cases with Familial Glucocorticoid Deficiency Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-11 Ying Duan, Yu Xia, Zhuwen Gong, Huili Liu, Lili Liang, Kaichuang Zhang, Yi Yang, Ruifang Wang, Bing Xiao, Wenjuan Qiu
Background: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by glucocorticoid deficiency without mineralocorticoid deficiency. We report 3 Chinese patients with MRAP or MC2R mutations. Case Reports: Patient 1 presented with hyperpigmentation. Endocrine investigations revealed low serum cortisol levels and elevated adrenocorticotropic hormone (ACTH) levels
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Left Ventricular Systolic Dysfunction Related to Adrenal Insufficiency in a Case due to Autoimmune Polyendocrine Syndrome Type 1 with a Novel Variant Mol. Syndromol. (IF 1.1) Pub Date : 2022-10-06 Yavuz Özer, Hande Turan, Aydilek Dağdeviren Çakır, Selman Gökalp, Zeynep Ocak, Oya Ercan, Olcay Evliyaoğlu
Introduction: Primary adrenal insufficiency associated with cardiomyopathy has been rarely reported in children. We report a case of left ventricular (LV) systolic dysfunction related to adrenal insufficiency with autoimmune polyendocrine syndrome type 1 (APS1). Case Presentation: A 7-year-old girl presented with a loss of consciousness. She had hyperpigmentation over joints and enamel hypoplasia.
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Homozygous Missense Variant in the N-Terminal Region of ANK3 Gene Is Associated with Developmental Delay, Seizures, Speech Abnormality, and Aggressive Behavior Mol. Syndromol. (IF 1.1) Pub Date : 2022-09-30 Muhammad Younus, Memoona Rasheed, Zhaohan Lin, Saeed A. Asiri, Ibrahim A. Almazni, Mohammed Ali Alshehri, Sarfraz Shafiq, Imran Iqbal, Amjad Khan, Hanif Ullah, Muhammad Umair, Ahmed Waqas
Introduction: Intellectual disability (ID) is a lifelong disability that affects an individual’s learning capacity and adaptive behavior. Such individuals depend on their families for day-to-day survival and pose a significant challenge to the healthcare system, especially in developing countries. ID is a heterogeneous condition, and genetic studies are essential to unravel the underlying cellular
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Prenatal Diagnosis of Intragenic HNF1B Variant-Associated Renal Disease by Exome Sequencing Mol. Syndromol. (IF 1.1) Pub Date : 2022-09-15 Qiu-Xia Yu, Xiang-Yi Jing, Dong-Zhi Li
Introduction: HNF1B-associated diseases are a group of genetic conditions that affect the kidney as well as other organ systems. Kidney anomalies are the most common symptoms. Other defects may include early-onset diabetes, genital abnormalities, and abnormalities of pancreas and liver function. Renal involvement has emerged as the earliest finding in HNF1B disease, even in prenatal life, with the
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Cerebellar Hypoperfusion in Two Patients with Cornelia de Lange Syndrome with Novel NIPBL Variants Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-25 Koji Obara, Erika Abe, Shigeo Mamiya, Itaru Toyoshima
Introduction: Cornelia de Lange syndrome (CdLS) is a rare congenital malformation characterized by distinctive facial features, short stature, and limb defects. In addition, half of the patients with CdLS exhibit repetitive self-injurious behaviors (SIBs) related to intellectual disability with autistic traits. CdLS is caused by pathogenic variants of genes encoding the cohesin complex pathway, with
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Ocular Manifestations of Hurler-Scheie Syndrome: Recurrence of Host Disease in the Corneal Transplant Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-22 Zsófia Kölkedi, Adrienne Csutak, Eszter Szalai
Introduction: Hurler-Scheie syndrome is a type of mucopolysaccharidosis I (MPS). In MPS I the decreased activity of alpha-L-iduronidase lysosomal enzyme leads to glycosaminoglycan (GAG) deposition in the intra- and extracellular matrix. Excessive amounts of GAG can accumulate in most layers of the cornea, including epithelial cells, stromal keratocytes, and endothelial cells. Case Presentation: A 25-year-old
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Diverse Clinical Manifestations of Cardiofaciocutaneous Syndrome Type 3 in Two Patients from South East Asia Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-21 Elyn Y.-L. Tzen, Jiin Yin Lim, Sue Mei Cheah, Jonathan T.L. Choo, Sylvia Kam, Zhi Min Ng, Biju Thomas, Saumya Jamuar, Ai Ling Koh, Ene-Choo Tan
Background: Cardiofaciocutaneous syndrome (CFCS) is a rare genetic condition caused by mutations in BRAF, KRAS, MAP2K1, or MAP2K2. It is characterized by ectodermal abnormalities, cardiac defects, intellectual disability, and distinct craniofacial features. CFCS falls under a group of conditions caused by mutations in the RAS/MAPK pathway called RASopathies which share many features. In particular
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FBLN5-Related Cutis Laxa Syndrome: A Case with a Novel Variant and Review of the Literature Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-06 Aysel Tekmenuray-Unal, Ceren Damla Durmaz
Introduction: FBLN5-related cutis laxa is a very rare, autosomal recessive syndrome that is characterized by loose, wrinkled, and redundant skin, sagging cheeks, emphysema, aortic or pulmonary artery abnormalities, inguinal hernia, and diverticula of the gastrointestinal and urinary tract. Case Presentation: In this study, we report an 8-year-old Turkish girl with a novel homozygous missense variant
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De novo Pure Partial Trisomy 6p Associated with Facial Dysmorphism, Developmental Delay, Brain Anomalies, and Primary Congenital Hypothyroidism Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-06 Ayberk Türkyılmaz, Emine Ayça Cimbek, Alper Han Çebi, Elif Acar Arslan, Gülay Karagüzel
Introduction: Partial trisomy 6p is a rare chromosomal anomaly, characterized by low birth weight, developmental delay, craniofacial abnormalities, feeding difficulties, congenital heart defects, and renal abnormalities. Some of the partial trisomy 6p cases reported in the literature included partial monosomy of another chromosome. This is often due to the fact that one of the parents is a balanced
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The Expanding Phenotypic Spectrum of NUP188 Variants Points Toward Multiple Biological Pathways Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-06 Martin Poot
Mol Syndromol
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22q11 Copy Number Variations in a Brazilian Cohort of Children with Congenital Heart Disorders Mol. Syndromol. (IF 1.1) Pub Date : 2022-07-04 Maiara A. Floriani, Andressa S. Santos, Bruna L. Diniz, Andressa B. Glaeser, Paulo R. Gazzola Zen, Rafael F. Machado Rosa
Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence
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CLN3-Associated NCL Case with a Preliminary Diagnosis of Niemann Pick Type C Mol. Syndromol. (IF 1.1) Pub Date : 2022-06-21 Çiğdem Seher Kasapkara, Ahmet Cevdet Ceylan, Deniz Yılmaz, Oya Kıreker Köylü, Burak Yürek, Burcu Civelek Ürey, Mehmet Gündüz
Introduction: Neuronal ceroid lipofuscinoses (NCLs) are a broad class of inherited lysosomal storage disorders. Known mutations in at least 13 different genes can result in NCL with variable ages of onset, symptoms, and pathologic findings. Generally, these patients experience cognitive and motor decline, seizures, visual impairment, and premature death. Pathologically, NCL patients display heterogeneous
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SLC26A2/DTDST Spectrum: A Cohort of 12 Patients Associated with a Comprehensive Review of the Genotype-Phenotype Correlation Mol. Syndromol. (IF 1.1) Pub Date : 2022-06-15 Cynthia Silveira, Karina da Costa Silveira, Maria D. Lacarrubba-Flores, Maurício T. Sakata, Silvia N. Carbognani, Juan Llerena Jr., Carolina A. Moreno, Denise P. Cavalcanti
Introduction: Pathogenic variants in the SLC26A2/DTDST gene cause the following spectrum of phenotypes: achondrogenesis 1B (ACG1B), atelosteogenesis 2 (AO2), diastrophic dysplasia (DTD), and recessive-multiple epiphyseal dysplasia (rMED), the first 2 being lethal. Here, we report a cohort and a comprehensive literature review on a genotype-phenotype correlation of SLC26A2/DTDST-related disorders. Methods:
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COL7A1 Homozygous Arg2471Ter Mutation Leads to the Severe Phenotype of Autosomal Recessive Dystrophic Epidermolysis Bullosa in the Fetus Mol. Syndromol. (IF 1.1) Pub Date : 2022-06-14 Xuliang Zhao, Weiwei Sun, Zhihui Cui, Min Yu, Qi Wang, Pengcheng Wang, Ruixia Tian
Introduction: Autosomal recessive dystrophic epidermolysis bullosa (RDEB) is a rare disease with an early onset and severe phenotype. The pathogenic mechanism associated with mutations in the gene COL7A1 has been widely studied and many related cases have been reported, but prenatal cases are rare. Here, we report the prenatal diagnosis of a sporadic case of RDEB. Methods: In this study, the fetus