[ occurrence and contribution of germline BRCA1/2 sequence alterations in Iranian patients with breast cancer]

Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families. One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls. In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83[-TT], IVS8-70[-CATT], IVS2+9[G>C], IVS1-20[G>A], IVS1-8[A>G], p.Met1Ile, IVS2+24[A>G], IVS5-8 [A>G], IVS2[35-39]TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70[T>G], 1994-1995 [InsA] in BRCA2. Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments [42], 80% related to BRCA1 and 20% to mutations in BRCA2 genes

[Investigation of connexin 26 mutations and three large deletions spanning connexin 30 in 63 Iranian families with autosomal recessive non-syndromic hearing loss]

Hearing loss is the most frequent neurosensory defect in human. Mutations in GJB2 and GJB6 are responsible for 50% of autosomal recessive non-syndromic hearing loss [ARNSHL] cases. Here we report on the frequencies of GJB2 and GJB6 mutations and three large deletions spanning the GJB6 gene including Del [GJB6-D13S1830], Del [GJB6-D13S1854] and a>920 kb deletion in patients affected by ARNSHL referred to Kawsar's Human Genetics Research Center. In this study, 94 patients from 63 families with ARNSHL were investigated. Patient's homozygote for 35delG were screened and left out of the study and the remaining samples were analyzed by sequencing of GJB2 and GJB6 genes. Also the three large deletions spanning the GJB6 gene were analyzed by Real Time PCR In this study we found GJB2 mutations in 13 families [20.6%] out of 63.The 35delG mutation was the most common mutation in the studied population [61.5%]. Other GJB2 mutations were delE120, R127H, W24X, and V37I. The heterozygous or negative cases for the GJB2 mutations were screened for mutation in the GJB6 gene by sequencing and no mutation was observed. Also, we checked the three large deletions in GJB6, we found no mutations. Low frequency of mutations in the GJB2 gene implies that other genes may be involved in causing non-syndromic hearing loss in our country