Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar-onset neuropathy.
Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar-onset neuropathy.
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DOI：
10.1002/mus.25550
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发表时间：
2017-11
期刊：
影响因子：
3.4
通讯作者：
Traynor BJ
中科院分区：
文献类型：
--
作者：
Caress JB;Johnson JO;Abramzon YA;Hawkins GA;Gibbs JR;Sullivan EA;Chahal CS;Traynor BJ
进行性延髓运动神经病主要由延髓起病的肌萎缩侧索硬化症引起。遗传性IV型淀粉样变性也表现为类似运动神经元病的延髓神经病变。这种疾病只在芬兰流行，通常不包括在ALS的鉴别诊断中。我们研究了一个家族中的18名成员，其中一些人患有延髓运动神经病，并进行了外显子组测序。五个受影响的家庭成员被发现在GSN基因中有D187Y替换，已知会导致遗传性IV型淀粉样变性。这个美国家庭表现为进行性球神经病变，原因是在芬兰没有发现明胶蛋白突变。遗传性IV型淀粉样变性表现为球运动神经病变，而不是常见形式的淀粉样变性所致的周围神经病变。这份报告展示了外显子组测序的力量，以确定不完全或非典型表型的罕见遗传性疾病的原因。
Progressive bulbar motor neuropathy is primarily caused by bulbar-onset ALS. Hereditary amyloidosis type IV also presents with a bulbar neuropathy that mimicks motor neuron disease. The disease is prevalent in Finland only and is not commonly included in the differential diagnosis of ALS. We studied 18 members of a family in which some had bulbar motor neuropathy, and we performed exome sequencing. Five affected family members were found to have a D187Y substitution in the GSN gene known to cause hereditary amyloidosis type IV. This American family presented with progressive bulbar neuropathy due to a gelsolin mutation not found in Finland. Hereditary amyloidosis type IV presents with bulbar motor neuropathy and not with peripheral neuropathy as occurs with common forms of amyloidosis. This report demonstrates the power of exome sequencing to determine the cause of rare hereditary diseases with incomplete or atypical phenotypes.