Istituto di Neurologia, Università Cattolica del Sacro Cuore, Rome, Italy.
J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1201-3. doi: 10.1136/jnnp-2012-302897. Epub 2012 Jul 8.
To classify familial amyotrophic lateral sclerosis (FALS) on the base of family history, and to determine whether frequency of mutations in major amyotrophic lateral sclerosis (ALS) genes varies in different FALS categories.
Included in the study are 53 FALS families. Patients were classified as definite, probable and possible FALS, according to recently proposed criteria. Seven ALS-associated genes, including SOD1, TARDBP, FUS, ANG, ATXN2, OPTN and C9ORF72, were analysed.
Thirteen patients (24.5%) were included in the definite group. The great majority of our FALS cases (40/53, 75.5%) were families with only two affected relatives; of these, 31 (58.5%) were included in the probable, and 9 (17%) in the possible FALS categories. The percentage of mutations was 61.5% in definite, 41.9% in probable and 11.1% in possible FALS. With respect to probable FALS, if cases with parent-to-child transmission of the disease were considered separately, the mutational load increased to 61.5%, as observed in definite FALS.
Our findings provide evidence that frequency of mutations in currently known ALS genes varies widely among different FALS categories. Families with only two affected relatives have heterogeneous genetic components, the chance to detect mutations being higher in cases with parent-to-child transmission.
根据家族史对家族性肌萎缩侧索硬化症（FALS）进行分类，并确定主要肌萎缩侧索硬化症（ALS）基因的突变频率在不同的 FALS 类别中是否存在差异。
本研究纳入了 53 个 FALS 家族。根据最近提出的标准，将患者分为明确、可能和可疑 FALS。分析了 7 个与 ALS 相关的基因，包括 SOD1、TARDBP、FUS、ANG、ATXN2、OPTN 和 C9ORF72。
13 名患者（24.5%）被归入明确组。我们的大多数 FALS 病例（40/53，75.5%）为仅有两个受影响亲属的家族；其中，31 例（58.5%）归入可能 FALS，9 例（17%）归入可疑 FALS。明确 FALS 的突变率为 61.5%，可能 FALS 为 41.9%，可疑 FALS 为 11.1%。在可能 FALS 中，如果单独考虑有父母向子女遗传疾病的病例，突变负荷增加到 61.5%，与明确 FALS 相同。
我们的研究结果表明，目前已知 ALS 基因的突变频率在不同的 FALS 类别中差异很大。仅有两个受影响亲属的家族具有异质性遗传成分，有父母向子女遗传疾病的病例检测到突变的可能性更高。
