Benign hereditary chorea and deletions outside NKX2-1: What's the role of MBIP?
Benign hereditary chorea and deletions outside NKX2-1: What's the role of MBIP?
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DOI：
10.1016/j.ejmg.2018.03.011
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发表时间：
2018-10-01
影响因子：
1.9
通讯作者：
Ghezzi, Daniele
中科院分区：
文献类型：
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作者：
Invernizzi, Federica;Zorzi, Giovanna;Ghezzi, Daniele
NKX 2 -1基因的杂合子点突变或缺失导致良性遗传性舞蹈病（BHC）或原发性甲状腺功能减退症、呼吸窘迫和神经系统疾病的各种组合。在少数脑-肺-甲状腺综合征受试者中描述了NKX 2 -1近端但不包含的缺失。我们报告了一个三代意大利家庭，其中6名受试者表现为BHC，并携带邻近NKX 2 -1的基因组缺失，包括基因MBIP，最近提出与脑-肺-甲状腺综合征的发病机制相关。与对照组相比，我们观察到患者成纤维细胞中NKX 2 -1转录水平明显降低;这一发现表明MBIP缺失影响NKX 2 -1表达，模拟经典NKX 2 -1相关突变引起的单倍不足。
Heterozygous point mutations or deletions of the NKX2-1 gene cause benign hereditary chorea (BHC) or a various combinations of primary hypothyroidism, respiratory distress and neurological disorders. Deletions proximal to, but not encompassing, NKX2-1 have been described in few subjects with brain-lung-thyroid syndrome. We report on a three-generation Italian family, with 6 subjects presenting BHC and harboring a genomic deletion adjacent to NKX2-1 and including the gene MBIP, recently proposed to be relevant for the pathogenesis of brain-lung-thyroid syndrome. We observed a clear reduction of NKX2-1 transcript levels in fibroblasts from our patients compared to controls; this finding suggests that MBIP deletion affects NKX2-1 expression, mimicking haploinsufficiency caused by classical NKX2-1 related mutations.