Further delineation of the phenotype caused by a novel large homozygous deletion of GRID2 gene in an adult patient.

Different mutations in glutamate receptor ionotropic delta 2 (GRID2) gene cause cerebellar ataxia in human. We report the largest homozygous deletion of the GRID2 gene reported to date, most probably causing complete loss of the gene product. Our patient presents mainly early onset cerebellar ataxia, cerebellar atrophy, nystagmus, and developmental delay with the least amount of intellectual disability.

Identification of a novel deletion within ALDH3A2 gene in an Iranian Family with Sjögren-Larsson Syndrome.

Sjögren-Larsson syndrome (SLS) is a rare type of congenital ichthyosis with neurological problems and intellectual disability. Homozygous mutations in ALDH3A2 gene are known to be responsible for this syndrome. Here, we report an Iranian family with congenital SLS bearing a novel two-base-pair deletion within ALDH3A2 genomic sequence. Our finding expands the mutation spectrum of ALDH3A2 that is applicable for further molecular studies and management of SLS.

Finding mutation within non-coding region of GJB2 reveals its importance in genetic testing of hearing loss in Iranian population.

OBJECTIVE: Hereditary hearing loss is the most common neurosensory disorder in humans. Half of the cases have genetic etiology with extraordinary genetic heterogeneity. Mutations in one gene, GJB2, are the most common cause for autosomal recessive non-syndromic hearing loss (ARNSHL) in many different populations. GJB2 encodes a gap junction channel protein (connexin 26), and is located on DFNB1 locus on chromosome 13q12.11 which also involve another connexin gene, GJB6. Mutation screening of GJB2 revealed that a high number of patients with deaf phenotype have heterozygous genotype and carry only one mutant allele. As the first comprehensive study in Iran, we have targeted GJB2-related Iranian heterozygotes, looking for second mutant allele which leads to hearing impairment. They bear first mutation in their coding exon of GJB2. METHOD: Using PCR-based direct sequencing, we assessed 103 patients with ARNSHL for variants in non-coding exon and promoter region of this gene, for the first time in Iran. RESULT: We have identified the second mutant allele in splice site of exon-1 of GJB2 which is known as IVS1+1G>A in 17 probands. We found no mutation in promoter region of GJB2. CONCLUSION: Our findings reveal that IVS1+1G>A mutation in noncoding exon of GJB2 is the most common mutation after 35delG within multi ethnical Iranian heterozygote samples. It emphasizes to approach exon1 of GJB2 in case of ARNSHL genetic diagnosis.

The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss--a twelve year study.

OBJECTIVE: Mutations in GJB2, encoding connexin 26 (CX26), are causally related to autosomal recessive form of non-syndromic hearing loss (NSHL) at the DFNB1 locus and autosomal dominant NSHL at the DFNA3 locus. In this study, we investigated the prevalence of GJB2 mutations in the Iranian deaf population. METHODS: A total of 2322 deaf probands presenting the ethnically diverse Iranian population were screened for variants in GJB2. All persons were first screened for the c.35delG mutation, as this variant is the most prevalent GJB2-deafness causing mutation in the Iranian population. In all persons carrying zero or one c.35delG allele, exons 1 and 2 were then sequenced. RESULTS: In total, 374 (~16%) families segregated GJB2-related deafness caused by 45 different mutations and 5 novel variants. The c.35delG mutation was most commonly identified and accounts for ~65% of the GJB2 mutations found in population studied. CONCLUSION: Our data also show that there is a gradual decrease in the frequency of the c.35delG mutation and of GJB2-related deafness in general in a cline across Iran extending from the northwest to southeast.