Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

Tatsushi Tanaka, Kohei Aoyama, Atsushi Suzuki, Shinji Saitoh, Haruo Mizuno

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations. We enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH. We identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants. The prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

本文言語English
ページ(範囲)691-701
ページ数11
ジャーナルJournal of Pediatric Endocrinology and Metabolism
33
6
DOI
出版ステータスPublished - 02-06-2020

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

フィンガープリント 「Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル