Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1
Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1
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DOI：
10.1016/j.jpeds.2004.04.011
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发表时间：
2004-08-01
影响因子：
5.1
通讯作者：
Scavina, M
中科院分区：
文献类型：
--
作者：
Doyle, DA;Gonzalez, I;Scavina, M
目的 研究两个同父异母兄弟姐妹的 NKX2-1 基因，这些兄弟姐妹在状态筛查中促甲状腺激素 (TSH) 升高、足月妊娠后新生儿呼吸窘迫时间延长、持续性共济失调、构音障碍和发育迟缓。研究设计我们对受试者及其未受影响兄弟姐妹的血液或口腔拭子的 DNA 样本进行了扩增和测序。结果阻止外显子 2 和 3 剪接在一起的相同突变NKX2-1 基因存在于受影响的兄弟姐妹、他们的母亲和外祖母中，但不存在于未受影响的兄弟姐妹中。该突变以杂合形式存在，从而解释了该疾病的表型。 结论 NKX2-1 突变的常染色体显性遗传可能导致先天性甲状腺功能减退症、足月新生儿呼吸窘迫，以及多代受影响受试者的家庭中持续的神经系统症状，如共济失调、舞蹈手足徐动症和构音障碍。
Objective To study the NKX2-1 gene in two half-siblings with elevated thyroid-stimulating hormone (TSH) on state screen, prolonged neonatal respiratory distress despite term gestations, and persistent ataxia, dysarthria, and developmental delay.Study design We amplified and sequenced DNA samples from blood or buccal swab for subjects and their unaffected siblings.Results The same mutation that prevents splicing together of exons 2 and 3 of the NKX2-1 gene was present in the affected siblings, their mother, and maternal grandmother but not in their unaffected siblings. The mutation was present in the heterozygous form, thus explaining the disease phenotype.Conclusions Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.