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Horm Metab Res 2017; 49(09): 680-686
DOI: 10.1055/s-0043-110769
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Genetic Alterations in Pendrin (SLC26A4) Gene in Adult Hypothyroid Patients

Sourav Mukherjee
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
,
Manalee Guha
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
,
Bidisha Adhikary
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
,
Biswabandhu Bankura
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
,
Pubali Mitra
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
,
Subhankar Chowdhury
2   Department of Endocrinology, Institute of Post Graduate Medical Education & Research, Kolkata, West Bengal, India
,
Madhusudan Das
1   Department of Zoology, University of Calcutta, Kolkata, West Bengal, India
› Author Affiliations
Further Information

Publication History

received 31 December 2016

accepted 03 May 2017

Publication Date:
17 July 2017 (online)

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Abstract

Current study was aimed to screen the SLC26A4 gene in 127 nonautoimmune and noncongenital hypothyroid patients, who were under optimal iodine nutrition and devoid of any characteristics of Pendred syndrome from eastern part of Indian population. 8 single nucleotide variants/mutations were identified in heterozygous state in 20% patient population, which include 1 novel nonsynonymous (p.C18S), 1 novel intronic (g.942C>A), 3 known nonsynonymous (p.S23X, p.V239D, and p.I455F), and 3 known intronic (g.23034G>T, g.29641C>G, and g.33893T>C) variants. Only g.23034G>T was noted also in homozygous state in 2% patient population. However, Controls exhibited only the variations g.23034G>T and p.I455F. Therefore, present study reports for the first time that the observed novel variants in pendrin gene might be linked with autoimmune negative hypothyroidism, without any characteristics of Pendred syndrome and/or congenital hypothyroidism. While, all observed known variants/mutations were reported with either Pendred syndrome and/or congenital hypothyroidism earlier, but never with nonautoimmune adult hypothyroidism solely. Thereby, the absence of any features of Pendred syndrome and/or congenital hypothyroidism in patients with observed known nonsynonymous variants/mutations may be due to either heterozygous state of each variant or differential domain specific activity of ions trafficking in the respective organ. The analysis of amino acid change at least for p.C18S, p.S23X, and p.V239D in correlation with phenotypic characteristics of respective patients might assume a possible effect on protein structure and function. Altogether, we report for the first time that genetical variations in SLC26A4 gene could play an important role in development of nonautoimmune adult hypothyroidism.

Key words

adult hypothyroidism - pendrin - polymorphisms - mutations - India - SLC26A4

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