Homozygous DUOXA2 mutation (p.Tyr138*) in a girl with congenital hypothyroidism and her apparently unaffected brother: Case report and review of the literature

Endocrine journal

Shinji Higuchi¹  Chiho Sugisawa²  Tomonobu Hasegawa³  Masaki Takagi³  Matsuo Taniyama³  Kiyomi Abe⁵  Satoshi Narumi⁵  Yukihiro Hasegawa⁵ 

[1] Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan;Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan;Division of Endocrinology and Metabolism, Tokyo Metropolitan Children’Tokyo Health Service Association, Tokyo 162-8402, Japan;s Medical Center, Tokyo 183-8561, Japan

关键词: Congenital hypothyroidism;    DUOXA2;    Mutation;    Genetics;    Newborn screening;   

DOI  :  10.1507/endocrj.EJ16-0564

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Mutations in DUOXA2, encoding dual oxidase maturation factor 2, is a rare genetic cause of congenital hypothyroidism.Only four biallelic DUOXA2 mutation carriers have been described to date.This study was conducted to report the clinical and genetic findings of a DUOXA2 mutation-carrying family, and to review the previously reported cases.The proband was a 4-year-old girl, who was diagnosed as having congenital hypothyroidism in the frame of newborn screening.She had a high serum TSH level (138 mU/L) and a low free T4 level (0.4 ng/dL).Ultrasonography revealed goiter.She was immediately treated with levothyroxine.At age 3 years, reevaluation of her thyroid function showed a slightly elevated serum TSH level (11.0 mU/L) with normal free T4 level.Screening of the eleven congenital hypothyroidism-related genes demonstrated a previously reported nonsense DUOXA2 mutation (p.Tyr138*) in the homozygous state.Unexpectedly, we also found that the elder brother of the proband, who had no significant past medical history, had the identical homozygous mutation.Using expression experiments with HEK293 cells, we confirmed that p.Tyr138* was a loss-of-function mutation.In the literature, clinical courses of three patients were described, showing characteristic age-dependent improvement of the thyroid function.In conclusion, The proband showed comparable clinical phenotype to previously reported cases, while her brother was unaffected.The phenotypic spectrum of DUOXA2 mutations could be broader than currently accepted.

【 授权许可】

Unknown