Genetics and management of congenital hypothyroidism
Genetics and management of congenital hypothyroidism
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DOI：
10.1016/j.beem.2018.05.002
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发表时间：
2018-08-01
影响因子：
7.4
通讯作者：
Fugazzola, Laura
中科院分区：
文献类型：
--
作者：
Persani, Luca;Rurale, Giuditta;Fugazzola, Laura
一些证据支持先天性甲状腺功能减退症（CH）的相关遗传起源，但家族形式是罕见的。CH可归因于形态发生或功能缺陷，并且几个基因最初与甲状腺发育不全或激素生成障碍相关，具有高度可变的表达性和遗传缺陷的经常不完全突变。表型驱动的遗传分析很少在超过10%的情况下产生积极的结果，从而引起怀疑的遗传起源CH。然而，最近的无监督方法与系统的下一代测序（NGS）分析显示，这些候选基因的亚型等位基因的存在，其组合可以解释CH的情况下的显着部分。甲状腺功能减退表型与多个基因变异的家系共分离研究证实了CH的潜在寡基因起源，这最终代表了这种疾病的频繁散发发生的一个合适的解释。(C)2018爱思唯尔有限公司版权所有
Several evidences support a relevant genetic origin for Congenital Hypothyroidism (CH), however familial forms are uncommon. CH can be due to morphogenetic or functional defects and several genes have been originally associated either with thyroid dysgenesis or dyshormonogenesis, with a highly variable expressivity and a frequently incomplete penetrance of the genetic defects. The phenotype-driven genetic analyses rarely yielded positive results in more than 10% of cases, thus raising doubts on the genetic origin of CH. However, more recent unsupervised approaches with systematic Next Generation Sequencing (NGS) analysis revealed the existence of hypomorphic alleles of these candidate genes whose combination can explain a significant portion of CH cases. The co-segregation studies of the hypothyroid phenotype with multiple gene variants in pedigrees confirmed the potential oligogenic origin of CH, which finally represents a suitable explanation for the frequent sporadic occurrence of this disease. (C) 2018 Elsevier Ltd. All rights reserved.