Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Identification of a de novo mutation (H435Y) in the THRB gene in a Korean patient with resistance to thyroid hormone

갑상선호르몬 수용체 베타 유전자 돌연변이(H435Y)가 확인된 갑상선호르몬 저항성 증후군 1례

  • Shin, Jin Young (Department of Pediatrics, Catholic University of Daegu School of Medicine) ;
  • Ki, Chang-Seok (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jin Kyung (Department of Pediatrics, Catholic University of Daegu School of Medicine)
  • 신진영 (대구가톨릭대학교 의과대학 소아과학교실) ;
  • 기창석 (성균관대학교 의과대학 삼성서울병원 진단검사의학과학교실) ;
  • 김진경 (대구가톨릭대학교 의과대학 소아과학교실)
  • Received : 2007.03.12
  • Accepted : 2007.04.13
  • Published : 2007.06.15
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Abstract

The syndrome of resistance to thyroid hormone (RTH) is characterized by reduced tissue sensitivity to thyroid hormone (TH). In the majority of subjects, RTH is caused by mutations in the thyroid hormone receptor beta ($TR{\beta}$) gene, located on the chromosome locus 3p24.3. RTH is inherited in an autosomal dominant manner. The clinical presentation of RTH is variable, but common features include elevated serum levels of thyroid hormone (TH), a normal or slightly increased thyrotropin (thyroid stimulating hormone, TSH) level that responds to thyrotropin releasing hormone (TRH), and goiter. We report a 4 year-old girl, who was clinically euthyroid in spite of high total and free $T_4$, and $T_3$ concentrations, while TSH was slightly increased. Sequence analysis of the thyroid hormone receptor beta gene (THRB) confirmed a heterozygous C to T change at nucleotide number 1303, resulting in a substitution of histidine by tyrosine at codon 435 (H435Y). Further analysis of her parents revealed that the H435Y variation was a de novo mutation since neither parents had the variation. Her parents' TH and TSH levels were within normal range.

갑상선 호르몬 저항성 증후군은 갑상선 호르몬에 대한 조직의 반응이 감소되어 나타나는 드문 유전 질환이다. 대부분은 갑상선 호르몬 수용체 (TR) 유전자의 돌연변이로 인한 갑상선 호르몬 수용체의 결함에 의한다. TR 유전자의 변이는 일반적으로 이형접합성이며 상염색체 우성 유전 양상을 보인다. 혈청 갑상선 호르몬 수치가 증가되어 있음에도 불구하고 혈청 갑상선 자극호르몬 수치가 억제되지 않으며, 임상 양상은 다양하다. 본 증례는 경미한 갑상선종, 총 및 유리 $T_4$, $T_3$의 증가, 정상 범위의 TSH 소견을 보이는 4세 여아로서 TR 유전자 분석에서 과오돌연변이(H435Y)를 확인하였다. 부모에서는 돌연변이가 관찰되지 않았으며, 갑상선 기능도 정상이었다. 특별한 투약 없이 추적 관찰 중에 갑상선종의 증가나 다른 증상의 악화는 없는 상태이다.

Keywords

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