Exome sequencing reveals novel BCS1L mutations in siblings with hearing loss and hypotrichosis
| Autor: | Huijun Wang, Jinghua Yin, Jianguo Zhang, Xu Cao, Lanlan Dai, Liu Xuanzhu, Zhimiao Lin, Lina Duo, Jie Zhang, Jiahui Zhao, Yong Yang, Zhanli Tang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Mitochondrial Diseases Adolescent Hearing Loss Sensorineural DNA Mutational Analysis Mutation Missense Biology Hypotrichosis Compound heterozygosity Bioinformatics Connexins Electron Transport Complex III symbols.namesake Genetics medicine Humans Missense mutation Child Hearing Loss Exome Exome sequencing Sanger sequencing Björnstad syndrome General Medicine medicine.disease Connexin 26 Codon Nonsense symbols biology.protein ATPases Associated with Diverse Cellular Activities Female Hair Diseases GJB6 |
| Zdroj: | Gene. 566:84-88 |
| ISSN: | 0378-1119 |
| Popis: | As a powerful tool to identify the molecular pathogenesis of Mendelian disorders, exome sequencing was used to identify the genetic basis of two siblings with hearing loss and hypotrichosis and clarify the diagnosis. No pathogenic mutations in GJB2, GJB3 and GJB6 genes were found in the siblings. By analysis of exome of the proband, we identified a novel missense (p.R306C) mutation and a nonsense (p.R186*) mutation in the BCS1L gene. Mutations were confirmed by Sanger sequencing. The siblings were compound heterozygotes, and the inheritance mode of autosomal recessive was postulated. BCS1L is the causative gene of Björnstad syndrome, which is characterized by sensorineural hearing loss and pili torti. The longitudinal gutters along the hair shaft were found by scanning electron microscopy in our patient. Therefore the diagnosis of Björnstad syndrome was eventually made for the patients. Our study extends the phenotypic spectrum of Björnstad syndrome and highlights the clinical applicability of exome sequencing as a diagnostic tool for atypical Mendelian disorders. |
| Databáze: | OpenAIRE |
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