Audit of the Congenital Hypothyroidism Screening Program in 15 Provinces of Iran.

BACKGROUND: The newborn screening (NBS) program for congenital hypothyroidism (CH) was launched on a national scale in Iran since 2005; we evaluated the program in 15 provinces, from 2011 to 2014. METHODS: Fifteen provinces, including 17 districts, were included in the study. Aggregated data of screening, diagnosis, and management of all neonates born in each district in 2011 were retrospectively gathered and collectively analyzed. RESULTS: Program coverage ranged from 77 to 100% in different districts. The positive predictive value was low and widely ranged from 1.3 to 15.5. Transient congenital hypothyroidism (TCH) distribution values were over 5 mU/L in more than 3% of the population and were reported in 9 out of 17 districts. Repeated screening test due to inappropriate sampling varied from 0.9% in Lorestan to 36% in Zabol. Recall rate varied from 0.16 in Ardebil to 1.58 in Zanjan. CH incidence was high, with the highest value being observed in Zanjan (1:241 newborns). Screening age at 3-5 days from birth were highly observed in Gonabad (95.2%) and Zanjan (94.5%), with the lowest values observed in Giroft, Zabol, Kerman and Tehran. CH treatment was initiated before 40 days of age in 90.6% of cases. Survival time for TSH normalization event varied among the districts from 25 to 163 days. After withholding treatment at 3 years of age, TCH was identified in 30%-60% of hypothyroid cases. CONCLUSION: Main indicators of the screening program have reached the optimal goals defined by the Ministry of Health and Medical Education. However, high false positive rate and non-optimal neonatal TSH distribution values necessitate readdressing these challenging issues.

Insulin receptor gene mutations in iranian patients with type II diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus type II suffer from hyperglycemia because they are not able to use the insulin that they produce, often due to inadequate function of insulin receptors. There are some evidences that this deficiency is inherited in a dominant autosomal manner and leads to the malfunction of the pancreatic beta cells resulting in insulin excretion disorders. In this study, we sought to identify mutations in the insulin receptor (INSR) gene, which can cause insulin resistance in type II diabetic patients. METHODS: DNA was extracted from peripheral blood cells of the patients (n = 128) diagnosed with type II diabetes. All 22 exons of the INSR gene of the patients were analyzed for mutations running PCR, conformation-sensitive gel electrophoresis and DNA sequencing, consecutively. RESULTS: Approximately 26% of the patients had genetic mutations; however, most of them were not reported. These mutations include exon 2 (His171Asn, Ile172Ser, Cys196Ser and Ser210Arg), exon 3 (Gly227Asp and Gly232Ser), exon 8 (Thr543Ser), exon 9 (a heterozygote was observed with no change in phenylalanine at position 669), exon 13 (two heterozygotes: Arg890Pro with Asn865 remaining unchanged), exon 14 (Ala906Gly and Pro918Trp with Arg902 unchanged), exon 17 (Val1086Glu) and exon 19 (His1157Gln with Thr1172 unchanged). CONCLUSION: The lack of similar mutation records in literature and genetic data banks may suggest a geographic pattern for these INSR gene variants in our population.

Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment.

Mutations in the SLC26A4 gene at the DFNB4 locus are responsible for Pendred syndrome and non-syndromic hereditary hearing loss (DFNB4). This study included 80 nuclear families with two or more siblings segregating presumed autosomal recessive hearing loss. All deaf persons tested negative for mutations in GJB2 at the DFNB1 locus and were, therefore, screened for autozygosity by descent (ABD) using short tandem repeat polymorphisms (STRPs) that flanked SLC26A4. In 12 families, homozygosity for STRPs suggested possible ABD in this genomic region. Affected individuals in five families had a positive perchlorate discharge test. Sequence analysis of SLC26A4 identified ten mutations in eight families (T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA and L445W), of which, four are novel (T420I, G334V, 965insA and R79X). These results imply that Pendred syndrome is the most prevalent form of syndromic hereditary hearing loss in Iran.