Homozygous DUOXA2 mutation (p.Tyr138*) in a girl with congenital hypothyroidism and her apparently unaffected brother: Case report and review of the literature.
Homozygous DUOXA2 mutation (p.Tyr138*) in a girl with congenital hypothyroidism and her apparently unaffected brother: Case report and review of the literature.
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DOI：
10.1507/endocrj.ej16-0564
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发表时间：
2017-06
影响因子：
2
通讯作者：
Chiho Sugisawa;Shinji Higuchi;M. Takagi;Y. Hasegawa;M. Taniyama;K. Abe;T. Hasegawa;S. Narumi
中科院分区：
文献类型：
--
作者：
Chiho Sugisawa;Shinji Higuchi;M. Takagi;Y. Hasegawa;M. Taniyama;K. Abe;T. Hasegawa;S. Narumi
编码双氧化酶成熟因子2的DUOXA2突变是先天性甲状腺功能减退的一种罕见的遗传原因。到目前为止，只有四个双等位基因DUOXA2突变携带者被描述。本研究旨在报道一个DUOXA2突变携带者家系的临床和遗传学结果，并回顾以前报道的病例。先证者是一名4岁女孩，在新生儿筛查中被诊断为先天性甲状腺功能减退症。血清TSH水平较高(138mU/L)，游离T4水平较低(0.4 ng/dL)。超声检查发现有甲状腺肿大。她立即接受了左旋甲状腺素的治疗。3岁时复查甲状腺功能，血清TSH轻度升高(11.0 mU/L)，游离T4正常。对11个先天性甲状腺功能减退症相关基因的筛查显示，先前报道的DUOXA2无义突变(p.Tyr138*)处于纯合状态。出乎意料的是，我们还发现先证者的哥哥，没有明显的病史，有相同的纯合子突变。通过对HEK293细胞的表达实验，我们证实了p.Tyr138*是一个功能丧失的突变。在文献中，描述了三名患者的临床病程，显示出甲状腺功能随年龄增长而改善的特点。总而言之，先证者的临床表型与以前报道的病例相似，而她的兄弟没有受到影响。DUOXA2突变的表型谱可能比目前接受的更广泛。
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.