High Frequency of D727E Polymorphisms in Exon 10 of the TSHR Gene in Brazilian Patients with Congenital Hypothyroidism

Abstract

Congenital Hypothyroidism affects between 1:3000 and 1:4000 newborn infants in iodinesufficient regions. Some studies have shown that mutations and polymorphisms in the TSH receptor gene are responsible for this disease. In the present study, mutations of exon 10 of the TSH receptor gene were investigated in Congenital Hypothyroidism patients. In the present study a sample of 90 Brazilian patients with primary congenital hypothyroidism was analyzed. Genomic DNA was isolated from peripheric blood samples. Exon 10 of the TSH receptor gene was amplified by PCR, and amplicons were automatically sequenced. Three nucleotide alterations were identified: c.1377G>A (A459A), c.1935G>A (L645L), and c.2181C>G (D727E). A459A polymorphism was also described previously in patients with thyroid cancer. The nucleotide alteration L645L was found in a single patient. This is the first time the L645L mutation has been described. D727E polymorphism showed high frequency (allele frequency 10%) in present study when compared to others reports.

Mutation screening in the genes PAX-8, NKX2-5, TSH-R, HES-1 in cohort of 63 Brazilian children with thyroid dysgenesis

“…Similar to our study, only a few mutations have previously been found in large panels of patients (18,23). Mutations have previously been identified in familial groups with TD, however, in our population there are likely to be sporadic and unrelated cases, which could be an important factor to evaluate the impact of these genetic variants at population level (28).…”

“…Four polymorphisms were found in the TSH-R gene: a) rs1991517 (g.81610583G>C) was found in 31/63 (49%) patients -27 heterozygotes, 4 homozygotes; b) rs2234919 (g.81422178C>A) was found in 4/63 (6%) -all heterozygotes; c) rs752184247 (g.78929481G>A) was found in 14/63 (22%) -all heterozygotes and; d) rs200551849 (g.8589551C>T) was found in 2/63 (3%) patientsboth compound heterozygotes with the rs1991517 polymorphism. (8,(20)(21)(22)(23)(24) were not responsible for the TD confirmed in our cohort. This finding implies that there may be other genes that are responsible for TD (6)(7)(8).…”