Neurological and Neuromuscular Rare disorders department, CERCA, University Hospital Center of Martinique, Martinique, France.
University Hospital Center of Paris, La Pitié Salpétrière Hospital, Paris, France.
Amyotroph Lateral Scler Frontotemporal Degener. 2021 Nov;22(7-8):545-551. doi: 10.1080/21678421.2021.1900870. Epub 2021 Mar 23.
Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disorder that causes degeneration of upper and lower motor neurons and their axons. ALS is mostly sporadic, but there are familial forms. In more than half of the familial forms, a pathogenic variant is found in one of the following genes: , , , , and . is the 2nd most common gene involved in genetic forms of ALS. Genotype-phenotype relationships are occasionally established in genetic forms of ALS associated with mutations pathogenic variants. The c.281G > T (p.[G93V]) variant in is associated with a rarely described and unexplained anticipation phenomenon. We report a large family from Martinique in whom ALS is associated with a c.281G > T (p.[G93V]) pathogenic variant in and a statistically suggested anticipation. A whole-exome study and detection of CNVs (CoDESeq) from 3 affected members of this family revealed the presence of variants of uncertain signification (VUS) in other ALS genes. VUS in and were present in patients of the 2nd generation, and CNVs involving and were found in the youngest case of the family.
肌萎缩侧索硬化症（ALS）是一种罕见的神经退行性疾病，导致上下运动神经元及其轴突变性。ALS 大多为散发性，但也有家族性形式。在超过一半的家族性形式中，以下基因之一存在致病性变异： ， ， ， ， 和 。 是与遗传形式 ALS 相关的第 2 常见基因。在与 突变相关的遗传形式 ALS 中，偶尔会建立基因型-表型关系。 中的 c.281G > T (p.[G93V]) 变异与一种很少描述和未解释的预期现象有关。我们报告了一个来自马提尼克岛的大家族，其中 ALS 与 中的 c.281G > T (p.[G93V]) 致病性变异有关，并存在统计学上的预期。对这个家族的 3 名受影响成员进行全外显子组研究和 CNV 检测（CoDESeq）发现，其他 ALS 基因存在意义不明的变异（VUS）。第 2 代患者存在 和 中的 VUS，而家族中最年轻的病例则发现了涉及 和 的 CNV。
