THRA基因的一种与甲状腺激素抵抗非典型表型相关的新突变。
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Espiard S, Savagner F, Flamant F, Vlaeminck-Guillem V, Guyot R, Munier M, d'Herbomez M, Bourguet W, Pinto G, Rose C, Rodien P, Wemeau JL
THRA基因的一种与甲状腺激素抵抗非典型表型相关的新突变。
中华内分泌杂志2015年8月;100(8):2841-8。doi: 10.1210 / jc.2015 - 1120。Epub 2015年6月2日。
- PubMed ID
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26037512 (PubMed视图］
- 摘要
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背景:RTHalpha是最近发现的对甲状腺激素(RTH)的耐药性，由于THRA的突变，基因编码TRalpha1，甲状腺激素受体。在一些生长迟缓、身材矮小和低游离T4/游离T3 (FT4/FT3)比值的患者中有报道。目的:研究一名27岁的侏儒症患者，患者的FT4/FT3比值较低。设计:收集临床、生化和放射学数据。对患者及其亲属进行了全外显子组测序。结果:患者表现为先天性大细胞贫血和严重骨畸形，并伴有生长迟缓、侏儒症、锁骨发育不全以及手指、脚趾和肘关节异常。成年后，她表现为行为活跃、慢性运动性腹泻和高钙血症。T3治疗导致心率加速、腹泻恶化和TSH抑制。T3恢复正常的低休息能量消耗。rT3、SHBG、IGF-1正常。 A de novo monoallelic missense mutation in THRA was discovered, the N359Y amino acid substitution (c.1075A>T), which affected both the TRalpha1 and the non-receptor isoform TRalpha2. The mutant TRalpha1 had a decrease in transcriptional activity related to decreased T3 binding and a dominant-negative effect on the wild-type receptor. CONCLUSIONS: This patient presents a new phenotype including more significant bone abnormalities, lower TSH, and higher FT3 levels, without certainty of all her symptoms with the TRalpha1(N359Y) mutation. This case suggests that patients with a low FT4/FT3 ratio should be screened for THRA mutations, even if clinical and biological features differ from previous reported cases of RTHalpha.