Novel CFTR mutations in two Iranian families with severe cystic fibrosis

Background: Cystic fibrosis [CF] is a common autosomal recessive disorder that affects many body systems and is produced by mutations in the cystic fibrosis transmembrane conductance regulator [CFTR] gene. CF is also the most frequently inherited disorder in the West. The aim of this study was to detect the mutations in the CFTR gene in two Iranian families with CF

Methods: After DNA extraction using the salting out method, a mutation panel consisting of 35 common mutations was tested by PCR, followed by reverse hybridization Strip Assay. To confirm the mutations, we have also performed Sanger sequencing for all 27 exons, intronic flanking regions, and 5' and 3' UTRs of the CFTR gene

Results: Carrier testing in a spouse revealed a novel nonsense mutation in the CFTR gene [c.2777 T>A [p.L926X]] in exon 17 for husband and a previously described heterozygous splice site pathogenic mutation [c.1393-1G>A] in his wife. The other novel compound heterozygous missense mutation [c.3119 T>A [p.L1040H]], which was previously reported as nonsense c.3484C>T [p.R1162X] mutation, was found in exon 19 in patient screening

Conclusion: Two novel CFTR mutations in exons 17 and 19 are responsible for CF with severe phenotypes in two Iranian families. These two mutations supplement the mutation spectrum of CFTR and may contribute to a better understanding of CFTR protein function

Association study of the TREM2 gene and identification of a novel variant in Exon 2 in Iranian patients with Late-Onset Alzheimer's disease

Objective: To analyze the association between TREM2 exon 2 variants and late-onset [sporadic] Alzheimer's disease [AD] in an elderly Iranian population

Materials and Methods: Exon 2 of TREM2 in a total of 131 AD patients and 157 controls was genotyped using polymerase chain reaction and Sanger sequencing. Fisher's exact test was used to compare the allele and genotype frequency between the 2 study groups

Results: One homozygous and 2 heterozygous carriers of rs75932628-T in the AD patients and 1 heterozygous carrier in the control group were identified. One novel damaging variant, G55R, was also detected in the AD patient group. The frequency of rs75932628-T as well as the amount of rare variants were higher in the AD patients than in the controls, but this did not reach a statistically significant association with AD [odds ratio: 4.8; 95% confidence interval: 0.54 to 43.6; p = 0.270]

Conclusion: The rs75932628-T allele frequency in the elderly Iranian population [0.86%] was high

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

[Screening of GJB2 Mutations in autosomal recessive non-syndromic kashan deaf patients]

Hearing loss is the most common sensory neural defect in humans, affecting 1 of 1000/2000 neonates, with over half of these cases predicted to be hereditary in nature. Most hereditary hearing loss is inherited in a recessive fashion, accounting for approximately 80% of non-syndromic hearing loss [NSHL]. Mutations in GJB2, encoding Connexin26, are major cause of inherited deafness in the most populations. We studied 34 probands from 34 families with autosomal recessive nonsyndromic hearing loss [ARNSHL] in Kashan populasions. Mutations Screening of GJB2 was performed by Amplification Refractory Mutation System [ARMS]-PCR for detection of 35delG and then we analyzed all samples excluding 35delG homozygote by DHPLC and Direct Sequencing.We identified 2 mutations [35delG 2.9%, 312de114 2.9%] and 2 polymorphisms V1531 in this study. Regards to our data,GJB2 mutations are very low in comparison with other part of world and finally, further studies need to find other genes that have a causal role in NSHL in this population