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DOI: 10.1055/s-0038-1676644
Gene Variants in NKX2-1 Do Not Represent a Major Etiological Factor of Primary Congenital Hypothyroidism in Mexican Population
Publikationsverlauf
04. September 2018
12. November 2018
Publikationsdatum:
02. Januar 2019 (online)
Abstract
Congenital hypothyroidism (CH), attributable to thyroid dysgenesis (TD), has an unusually high prevalence in Mexican population but the causes are unknown. NKX2-1, as a candidate gene, was subjected to automated Sanger sequencing in 122 unrelated Mexican patients with CH/TD. Although this study includes the largest number of TD-related CH patients in whom NKX2-1 has been analyzed, no pathogenic variants were detected; only three benign polymorphic changes were identified. These results suggest that NKX2-1 is not a major contributor to the etiology of CH or its high prevalence in Mexicans. Our work identifies misannotations of NKX2-1 variants in three previous published reports.
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References
- 1 Hinojosa-Trejo MA, Vela-Amieva M, Ibarra-González I. , et al. [Congenital hypothyroidism birth prevalence]. Acta Pediatr Mex 2018; SI (39) 5S-13S
- 2 Szinnai G. Genetics of normal and abnormal thyroid development in humans. Best Pract Res Clin Endocrinol Metab 2014; 28 (02) 133-150
- 3 Sun F, Zhang JX, Yang CY. , et al. The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes. Eur J Endocrinol 2018; 178 (06) 623-633
- 4 Kumorowicz-Czoch M, Madetko-Talowska A, Tylek-Lemanska D, Pietrzyk JJ, Starzyk J. Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification. J Pediatr Endocrinol Metab 2015; 28 (1-2): 171-176
- 5 Hishinuma A, Onigata K, Kuribayashi T, Ieiri T. Sequence analysis of thyroid transcription factor-1 gene reveals absence of mutations in patients with thyroid dysgenesis but presence of polymorphisms in the 5' flanking region and intron. Endocr J 1998; 45 (04) 563-567
- 6 Narumi S, Muroya K, Asakura Y, Adachi M, Hasegawa T. Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients. J Clin Endocrinol Metab 2010; 95 (04) 1981-1985
- 7 Perna MG, Civitareale D, De Filippis V, Sacco M, Cisternino C, Tassi V. Absence of mutations in the gene encoding thyroid transcription factor-1 (TTF-1) in patients with thyroid dysgenesis. Thyroid 1997; 7 (03) 377-381
- 8 Lapi P, Macchia PE, Chiovato L. , et al. Mutations in the gene encoding thyroid transcription factor-1 (TTF-1) are not a frequent cause of congenital hypothyroidism (CH) with thyroid dysgenesis. Thyroid 1997; 7 (03) 383-387
- 9 Wang F, Liu C, Jia X. , et al. Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis. Clin Chim Acta 2017; 470 (July): 36-41
- 10 Carré A, Castanet M, Sura-Trueba S. , et al. Polymorphic length of FOXE1 alanine stretch: evidence for genetic susceptibility to thyroid dysgenesis. Hum Genet 2007; 122 (05) 467-476
- 11 Alcántara-Ortigoza MA, González-del Angel A, Martínez-Cruz V. , et al. Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation. Clin Endocrinol (Oxf) 2012; 76 (01) 148-150
- 12 Long W, Lu G, Zhou W. , et al. Targeted next-generation sequencing of thirteen causative genes in Chinese patients with congenital hypothyroidism. Endocr J 2018; 65 (10) 1019-1028