[Screening of DFNB4 locus in Iranian families with hereditary hearing impairment]

Mutations in the SLC26A4 gene in the DFNB4 locus is responsible for syndromic [Pendred syndrome] and non-syndromic hereditary hearing loss [HHL]. In many populations, mutations in this gene have been reported as a second cause of HHL. The objective of this study was to investigate the prevalence of SLC26A4 mutations in our HHL consanguineous families. After completing clinical evaluation and obtaining signed consent forms from each family, we included 80 families with two or more affected individuals, referred to the Genetics Research Center [GRC]. All families that previously tested negative for the DFNB1 locus were candidates for homozygosity mapping using STRs for DFNB4 locus. Families localized to this region were subjected to complete DMA sequencing. Twelve out of 80 families were mapped to DFNB4. Sequence analysis of 12 linked families revealed 10 mutations in 8 families. [T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA, and L445W]. The T420I, G334V, L597S and R79X were novel mutations; we did not find any mutation in the four linked families, nor did we detect any nonsyndromic families with mutation in the SLC26A4 gene. We have been able to identify mutation in the SLC26A4 gene in only 8 of 80 families. In 12 families, we detected some degree of diffuse or nodular goiter; three out of 12 families showed thyroid function impairment and in five of 12 families there were positive prechlorate discharge tests. Eight families that showed mutation had normal temporal bone scan. This investigation, demonstrated that the SLC26A4 gene mutation is the most prevalent syndromic hereditary hearing loss in Iran, a finding in accordance with reports from other countries

[Preschool vision screening program: coverage, validity and outcome]

To evaluate the preschool vision screening program coverage and to assess its validity indices including specificity, negative predictive value [NPV], sensitivity and positive predictive value [PPV] and the frequency of treatment for visual impairment. A sample of 906 six-year-old children signed up for primary school registration in the Shahrood district [Semnan, Iran] were randomly selected and invited for optometric examination. Mentally retarded and blind subjects due to organic disorders were excluded. All children were examined by optometrists for ocular alignment, visual acuity, cover test, stereoacuity and retinoscopy under cycloplegia. Screening history and the results were detected by available documents. Treatment history was obtained from the family. Of 906 invited children, 827 [91.3%] participated in the study, of which 815 [98.6%] were eligible and cooperative. Fifty-two children [6.4%] had amblyogenic visual impairment. Screening coverage rate was 85.3% [95% confidence interval [CI], 82.9-87.7] which was unrelated to gender, residence in urban or rural area or parents' education but was greater in families with higher-thanaverage economic status [87.7% vs 81.9%, P<0.05]. The specificity and NPV of the screening exam were 95.4% [95%CI, 94.1-96.7] and 96.7% [95%CI, 95.3-98.1], respectively. Only 47.5% of children with amblyogenic factors were suspected on screening examination [sensitivity]. Of those with suspected exams, 38.8% had impairments in optometric examination [PPV]. All of those with a correct diagnosis of amblyogenic visual impairment on screening had been treated. A significant proportion of six-year-old children have amblyogenic vision impairment. Inadequate coverage and validity of the current screening program has prevented timely diagnosis and treatment of many of them