[Identification of nucleotide changes of two known causative genes [BRCA2 and STK11] of hereditary breast cancer in an Iranian family using exome sequencing]

Since the identification of the two highly penetrant dominantly inherited genes, BRCA1/2, in the 1990s, a number of other genes have been identified which account for approximately 25% of the genetic basis for hereditary breast cancer. At least 75% are unidentified. The goal of this study is to investigate the presence or absence of a recessive pattern of inheritance in this heterogeneous disease whose possibility has been previously discussed by researchers. In this study we used exome sequencing as the most recent approach for identification of the genetic basis of any disease. The results of exome sequencing were confirmed by Sanger sequencing. Although we did not find any homozygous mutation in this family, however a heterozygous 4bp deletion that led to a frame shift mutation was identified in exon 11 of the BRCA2 gene. Also identified was a heterozygous single nucleotide polymorphism in exon 9 of the STK11 gene. The rs80359352 variation identified in this family is one of the frequent pathogenic mutations in the BRCA2 gene that has been reported in the BIC database. This variation has been previously observed in other ethnic populations such as Caucasians, Hispanics and the Chinese. In this study, for the first time, we report this mutation in Iranian population and its segregation in hereditary breast cancer

Relative frequency of GJB2 gene mutations in autosomal recessive non-syndromic hearing loss [ARNSHL] patients in lurastan population

Congenital hearing loss with many genetic and environmental causes affecting 1 in 1000 newborns. Mutations in the GJB2 [Gap Junction Beta-2] gene encoding the gap junction protein connexin 26 have been established as the main cause of autosomal recessive non-syndromic hearing loss. The aim of this study was to study the frequency of GJB2 mutations in Lurastan non-syndromic deaf population using ARMS/PCR, DHPLC and direct sequencing. For this purpose, 106 chromosomes from 53 patients were studied. Eighteen chromosomes [17%] carry GJB2 mutations including 35delG, 314dell4, 512insAACG, -3170G>A, W24X, V95M and 510insCGAA. The last mutation is a novel GJB2 mutation, 35delG mutation was diagnosed in 10 chromosomes [9/4%]; 4 patients were homozygote and 2 patients were heterozygote. Also polymorphism VI531 were found in 3 families. This frequency is significantly higher compared to that of the whole population of Iran