<i>GJB2</i>Gene Related Nonsyndromic Hearing Loss in Mazandaran Province, North of Iran

Introduction: Congenital hearing loss is the most common sensory deficit in the world and mutations in GJB2 gene are the most common cause of deafness in many populations. Frequency of GJB2 mutations is estimated about 16% in Iran and varies among different provinces with a decreasing trend from north to south. The aim of this study was to investigate the frequency of GJB2 mutations in Mazandaran province, north of Iran, among non-syndromic hearing loss patients. Methods: 262 patients from 204 families participated in this study. After genomic DNA extraction, GJB2 gene analysis was carried out using DNA sequencing of both coding and non-coding regions by ABI 3130XL genetic analyzer. Results: 30.15% of all subjects showed mutations in GJB2 gene. Four mutations, including c.35delG (Gly12Valfs*), IVSI-1 + 1G > A, c.95G > A (Arg32His) and c.224 G > A (Arg75Gln) comprises 69.89% of all mutations in this study c.35delG and IVSI-1 were the most common mutations among patients respectively. Codon 75 mutation (c.224G > A. p: Arg75Gln) with autosomal dominant inheritance was seen in 7 cases from 3 families. 22 patients showed only one mutation in GJB2 gene and in 126 (48.09%) individuals, parents had a consanguineous marriage. Discussion: Frequency of GJB2 gene related hearing loss among patients was higher than average (16%) in this province. This study also showed a dominant inheritance pattern of GJB2 gene in this area. Consanguineous marriage also showed highly frequent among parents. More investigation needs to clarify cause of hearing loss in those 22 patients with one mutation in GJB2 gene, either two gene inheritance or another gene may be responsible for hearing loss.

Identification of a novel nonsense mutation in kyphoscoliosis peptidase gene in an Iranian patient with myofibrillar myopathy

Myofibrillar myopathies(MFMs)are rare genetic and slowly progressive neuromuscular disorders.Several pathogenic mutations have been reported in MFM-related genes including DES,CRYAB,MYOT,LDB3 or ZASP,FLNC,BAG3,FHL1 and DNAJB6.Although MFMs is commonly inherited in an autosomal dominant manner,the inheritance pattern and novel mutated genes are not thoroughly elucidated in some cases.Here,we report discovery of a novel nonsense mutation in a 29-year-old Iranian male patient with motor disorders and deformity in his lower limbs.His parents are second cousins.Hereditary Motor Sensory Neuropathy as initial genetic diagnosis was ruled out.Whole exome sequencing using NGS on Illumina Hi-Seq4000 platform was performed to identify the disease and possible mutated gene(s).Our data analysis identified a homozygous nonsense unreported c.C415T(p.R139X)variant on kyphoscoliosis peptidase(KY)gene(NM_178554:exon4).Sanger sequencing of this mutation has been performed for his other related family members.Sequencing and segregation analysis was confirmed the NGS results and autosomal recessive inheritance pattern of the disease.