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

Chiho Sugisawa, Shinji Higuchi, Masaki Takagi, Yukihiro Hasegawa, Matsuo Taniyama, Kiyomi Abe, Tomonobu Hasegawa, Satoshi Narumi

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)807-812
Number of pages6
JournalEndocrine Journal
Volume64
Issue number8
DOIs
Publication statusPublished - 2017

Keywords

  • Congenital hypothyroidism
  • DUOXA2
  • Genetics
  • Mutation
  • Newborn screening

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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