Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred Publisher Pubmed



Mohammadiasl J1 ; Pourreza MR2 ; Mohammadi A2 ; Eskandari A2 ; Mozafarjalali S3 ; Tabatabaiefar MA2, 4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Obstetrics and Gynecology, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Dermatological Science Published:2017


Abstract

Background Nail disorder nonsyndromic congenital (NDNC) is a very rare clinically and genetically heterogeneous disease inherited both in recessive or dominant modes. FZD6 is a component of Wnt-FZD signaling pathway in which recessive loss-of-function variants in the corresponding genes could lead to nail anomalies. Objective A large multiplex family with NDNC was referred for genetic counselling. Thorough genetic evaluation was performed. Methods PCR-Sanger sequencing was carried out for the coding exons and exon-intron boundaries of the FZD6 gene. Co-segregation analysis, in silico evaluation and computational protein modeling was accomplished. Results A homozygous 1 bp deletion variant, c.1859delC (p.Ser620Cysfs*75), leading to a truncating protein was found in the patient. Parents were heterozygous for the variant. The variant was found to be co-segreagting with the phenotype in the family. Computational analysis and protein modeling revealed its pathogenic consequence by disturbing the cytoplasmic domain structure and signaling through loss of phosphorylation residues. The variant met the criteria of being pathogenic according to the ACMG guideline. Conclusions This is the first report of the genetic diagnosis of NDNC in Iran. We also report a novel pathogenic variant. The study of the FZD6 gene is recommended as the first step in the diagnostic routing of the autosomal recessive NDNC patients with enlarged nails. © 2017 Japanese Society for Investigative Dermatology
Related Docs
View other Related Docs
1. Identification of Six Novel Mutations in Iranian Patients With Maple Syrup Urine Disease and Their in Silico Analysis, Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis (2016)
2. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
3. Catecholaminergic Polymorphic Ventricular Tachycardia (And Seizure) Caused by a Novel Homozygous Likely Pathogenic Variant in Casq2 Gene, Gene (2024)
4. Autozygosity Mapping of Methylmalonic Acidemia Associated Genes by Short Tandem Repeat Markers Facilitates the Identification of Five Novel Mutations in an Iranian Patient Cohort, Metabolic Brain Disease (2018)
5. Homozygosity Mapping and Direct Sequencing Identify a Novel Pathogenic Variant in the Cisd2 Gene in an Iranian Wolfram Syndrome Family, Acta Diabetologica (2020)
6. Genotype, Phenotype and in Silico Pathogenicity Analysis of Hexb Mutations: Panel Based Sequencing for Differential Diagnosis of Gangliosidosis, Clinical Neurology and Neurosurgery (2018)
7. Maple Syrup Urine Disease Mutation Spectrum in a Cohort of 40 Consanguineous Patients and Insilico Analysis of Novel Mutations, Metabolic Brain Disease (2019)
8. Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type Vi and Fanconi−Bickel Syndrome, Frontiers in Genetics (2021)
Experts (# of related papers)
View all Related Experts
Ali Reza Tavasoli (6)
Mahmoudreza Ashrafi (4)
Other Related Docs
9. The Spectrum of Atm Gene Mutations in Iranian Patients With Ataxia-Telangiectasia, Pediatric Allergy and Immunology (2021)
10. Rpe65 and Retinal Dystrophy: Report of New and Recurrent Mutations, Journal of Gene Medicine (2020)
11. Clinical and Molecular Findings of Autosomal Recessive Spastic Ataxia of Charlevoix Saguenay: An Iranian Case Series Expanding the Genetic and Neuroimaging Spectra, Cerebellum (2023)
12. Multigene Next-Generation Sequencing Panel Identifies Pathogenic Variants in Patients With Unknown Subtype of Epidermolysis Bullosa: Subclassification With Prognostic Implications, Journal of Investigative Dermatology (2017)
13. Genetic Testing of Leukodystrophies Unraveling Extensive Heterogeneity in a Large Cohort and Report of Five Common Diseases and 38 Novel Variants, Scientific Reports (2021)
14. Identification of a Novel Homozygous Gls Gene Variant Associated With Developmental and Epileptic Encephalopathy (Dee) Type 71, Neurogenetics (2024)
15. Functional Analysis of a Novel Splicing Mutation in the Mutase Gene of Two Unrelated Pedigrees, Cell Journal (2016)
16. Genotypes of European and Iranian Patients With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips, Blood Advances (2021)
17. Autosomal Recessive Congenital Ichthyosis: Genomic Landscape and Phenotypic Spectrum in a Cohort of 125 Consanguineous Families, Human Mutation (2019)
18. Type 1 Diabetes Genetic Risk Score Discriminates Between Monogenic and Type 1 Diabetes in Children Diagnosed at the Age of <5 Years in the Iranian Population, Diabetic Medicine (2019)
19. Whole Exome Sequencing Reveals a Xpnpep3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient, Iranian Biomedical Journal (2020)
20. A Novel Pathogenic Variant in the Mitf Gene Segregating With a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred, Molecular Syndromology (2017)
21. Use of Expanded Carrier Screening for Retrospective Diagnosis of Two Deceased Siblings With Van Maldergem Syndrome 2: Case Report, Asian Biomedicine (2022)
22. Alopecia Areata-Like Pattern of Baldness: The Most Recent Update and the Expansion of Novel Phenotype and Genotype in the Ctnnb1 Gene, Neurological Sciences (2023)
23. A Mutational Hotspot in the Lamp2 Gene: Unravelling Intrafamilial Phenotypic Variation and Global Distribution of the C.877C>T Variant: A Descriptive Study, Cell Journal (2024)
24. A Novel Compound Heterozygote Mutation in the Arsb Gene in a Patient With Maroteaux-Lamy Syndrome and Its Insilico Evaluation, Meta Gene (2018)
25. A Novel Pathogenic Variant in the Lrtomt Gene Causes Autosomal Recessive Non-Syndromic Hearing Loss in an Iranian Family, BMC Medical Genetics (2020)
26. Clinical Application of Next Generation Sequencing for Mendelian Disease Diagnosis in the Iranian Population, npj Genomic Medicine (2024)
27. Identification of Eleven Different Mutations Including Six Novel, in the Arylsulfatase B Gene in Iranian Patients With Mucopolysaccharidosis Type Vi, Molecular Biology Reports (2019)
28. Beta Thalassemia in 31,734 Cases With Hbb Gene Mutations: Pathogenic and Structural Analysis of the Common Mutations; Iran As the Crossroads of the Middle East, Blood Reviews (2016)
29. Exome Sequencing Reveals Novel Rare Variants in Iranian Familial Multiple Sclerosis: The Importance of Pold2 in the Disease Pathogenesis, Genomics (2021)
30. In Silico Analysis of Novel Mutations in Maple Syrup Urine Disease Patients From Iran, Metabolic Brain Disease (2017)
31. Crystallographic Modeling of the Pnpt1:C.1453A>G Variant As a Cause of Mitochondrial Dysfunction and Autosomal Recessive Deafness; Expanding the Neuroimaging and Clinical Features, Mitochondrion (2021)
32. Crb1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum, Iranian Biomedical Journal (2019)
33. Nckap1l Defects Lead to a Novel Syndrome Combining Immunodeficiency, Lymphoproliferation, and Hyperinflammation, Journal of Experimental Medicine (2020)
34. The First Iranian Patient With You-Hoover-Fong Syndrome and a Review of the Literature on 27 Cases: Expanding the Genotypic and Phenotypic Spectrum, Neurological Sciences (2024)
35. Expanding the Clinical and Neuroimaging Features of Nkx6-2-Related Hereditary Spastic Ataxia Type 8, European Journal of Medical Genetics (2020)