Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation is a Novel Defect in Thyroid Dyshormonogenesis.

Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation is a Novel Defect in Thyroid Dyshormonogenesis.

J Clin Endocrinol Metab. 2018 Mar 12;:

Authors: Zou M, Alzahrani AS, Al-Odaib A, Alqahtani MA, Babiker O, Al-Rijjal RA, BinEssa HA, Kattan WE, Al-Enezi AF, Al Qarni A, Al-Faham MSA, Baitei EY, Alsagheir A, Meyer BF, Shi Y

Abstract
Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000-4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied.
Objective: To identify mutation spectrum of CH-causing genes.
Methods: Fifty-five patients from 47 families were studied by next-generation-exome sequencing.
Results: Mutations were identified in 52.7% of patients (29/55) in the following 11 genes: TG, TPO, DUOX2, SLC26A4, SLC26A7, TSHB, TSHR, NKX2-1, PAX8, CDCA8, and HOXB3. Among 30 patients with thyroid dyshormonogenesis, biallelic TG mutations were found in 12 patients (40%), followed by biallelic mutations in TPO (6.7%), SLC26A7 (6.7%), and DUOX2 (3.3%). Monoallelic SLC26A4 mutations were found in two patients, one of them co-existing with two tandem biallelic deletions in SLC26A7. In 25 patients with thyroid dysgenesis, biallelic mutations in TSHR were found in 6 patients (24%). Biallelic mutations in TSHB, PAX 8, NKX2-1, or HOXB3 were found once in four different patients. A monoallelic CDCA8 mutation was found in one patient. Most mutations were novel including three TG, two TSHR, and one in each of DUOX2, TPO, SLC26A7, TSHB, NKX2-1, PAX8, CDCA8, and HOXB3. SLC26A7 and HOXB3 were novel genes associated with thyroid dyshormonogenesis and dysgenesis, respectively.
Conclusions: TG and TSHR mutations are the most common genetic defects in Saudi CH patients. The prevalence of other disease-causing mutations is low, reflecting the consanguineous nature of the population. SLC26A7 mutations appear to be associated with thyroid dyshormonogenesis.

PMID: 29546359 [PubMed - as supplied by publisher]

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