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Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I- symporter

Item Type:Article
Title:Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I- symporter
Creators Name:Neumann, S. and Willgerodt, H. and Ackermann, F. and Reske, A. and Jung, M. and Reis, A. and Paschke, R.
Abstract:Iodine deficiency is the most important etiological factor for euthyroid endemic goiter. However, family and twin pair studies also indicate a genetic predisposition for euthyroid simple goiter. In hypothyroid goiters several molecular defects in the thyroglobulin (TG), thyroperoxidase (TPO), and Na+/I- symporter (NIS) genes have been identified. The TSH receptor with its central role for thyroid function and growth is also a strong candidate gene. Therefore, we investigated a proposita with a relapsing euthyroid goiter and her family, in which several members underwent thyroidectomy for euthyroid goiter. Sequence analysis of the complementary DNA (cDNA) of the TPO and TSH receptor genes revealed several previously reported polymorphisms. As it is not possible to exclude a functional relevance for all polymorphisms, we opted for linkage analysis with microsatellite markers to investigate whether the candidate genes are involved in the pathogenesis of euthyroid goiter. The markers for the genes TG, TPO, and NIS gave two-point and multipoint logarithm of odds score analysis scores that were negative or below 1 for all assumed recombination fractions. As no significant evidence of linkage was found, we conclude that these candidate genes can be excluded as a major cause of the euthyroid goiters in this family. In contrast, we have found evidence for linkage of familial euthyroid goiter to the recently identified locus for familial multinodular nontoxic goiter (MNG-1) on chromosome 14q. The haplotype cosegregates clearly with familial euthyroid goiter. Our results provide the first confirmation for MNG-1 as a locus for nontoxic goiter.
Keywords:Carrier Proteins, Chromosome Mapping, Genetic Linkage, Goiter, Human Pair 14 Chromosomes, Iodide Peroxidase, Membrane Proteins, Nodular Goiter, Northern Blotting, Nucleic Acid Hybridization, Pedigree, Ribonucleases, Symporters, Thyroglobulin, Thyrotropin Receptors
Source:Journal of Clinical Endocrinology and Metabolism
ISSN:0021-972X
Publisher:Endocrine Society (U.S.A.)
Volume:84
Number:10
Page Range:3750-3756
Date:October 1999
Official Publication:https://doi.org/10.1210/jc.84.10.3750
PubMed:View item in PubMed

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