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Next-generation sequencing reveals a novel pathological mutation in the TMC1 gene causing autosomal recessive non-syndromic hearing loss in an Iranian kindred.
Sadeghian, Ladan; Tabatabaiefar, Mohammad Amin; Fattahi, Najmeh; Pourreza, Mohammad Reza; Tahmasebi, Parisa; Alavi, Zahra; Hashemzadeh Chaleshtori, Morteza.
Afiliación
  • Sadeghian L; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Tabatabaiefar MA; Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran; Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Fattahi N; Cilinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • Pourreza MR; Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
  • Tahmasebi P; Department of Biology, Faculty of Sciences, Ilam University, Ilam, Iran.
  • Alavi Z; Department of Genetics, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran.
  • Hashemzadeh Chaleshtori M; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Electronic address: mchalesh@yahoo.com.
Int J Pediatr Otorhinolaryngol ; 124: 99-105, 2019 Sep.
Article en En | MEDLINE | ID: mdl-31176026
OBJECTIVES: Hearing loss (HL) is the most common sensory-neural disorder with excessive clinical and genetic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of the disease with no specific genotype-phenotype correlation in most of the cases. Whole exome sequencing (WES) is a powerful tool to overcome the problem of finding mutations in heterogeneous disorders. METHODS: A comprehensive clinical and pedigree examination was performed on a multiplex family from Khuzestan province suffering from hereditary HL. Direct sequencing of GJB2 and genetic linkage analysis of DFNB1A/B was accomplished. WES was utilized to find possible genetic etiology of the disease. Co-segregation analysis of the candidate variant was done. High resolution melting analysis was applied to detect variant status in 50 healthy matched controls. RESULTS: Clinical investigations suggested ARNSHL in the pedigree. The family was negative for DFNB1A/B. WES revealed a novel nonsense mutation, c.256G > T (p.Glu86*), in TMC1 segregating with the phenotype in the pedigree. The variant was absent in the controls. CONCLUSION: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a large family. The novel nonsense TMC1 variant meets the criteria of being pathogenic according to the ACMG-AMP variant interpretation guideline.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pérdida Auditiva / Proteínas de la Membrana Tipo de estudio: Guideline / Prognostic_studies Límite: Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Int J Pediatr Otorhinolaryngol Año: 2019 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pérdida Auditiva / Proteínas de la Membrana Tipo de estudio: Guideline / Prognostic_studies Límite: Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Int J Pediatr Otorhinolaryngol Año: 2019 Tipo del documento: Article País de afiliación: Irán Pais de publicación: Irlanda