Deptartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Child Health, University of Genoa, Genoa, Italy,
Medical Genetics Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy,
Neurodegener Dis. 2018;18(5-6):310-314. doi: 10.1159/000497820. Epub 2019 Mar 20.
The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Twelve patients had mutations in the SOD1, TARDBP, MATR3, and FUS genes, while 10 patients carried the C9orf72 expansion. One female patient was found to carry the D348G mutation in MAPT, previously reported in an Italian family with lower motor neuron disease. Our patient presented both upper and lower motor neuron signs, early development of dyspnea, resting and kinetic tremor, and a slow disease course (> 11 years). The present case further broadens the clinical phenotype associated with MAPT mutations and suggests that, although rarely, MAPT mutations can cause ALS and, therefore, should be analyzed in ALS patients, especially in those with early breathing difficulties and long-lasting disease.
我们的研究目的是评估 MAPT 基因突变在纯运动神经元病（ALS）患者中的作用。通过下一代测序技术，对一个包含 23 个基因的多基因panel（包括已知与 ALS 和额颞叶痴呆相关的 MAPT 基因）进行分析，共纳入了 120 例无认知障碍的散发性和家族性 ALS 患者。同时还对 C9orf72 扩增的存在情况进行了研究。12 例患者的 SOD1、TARDBP、MATR3 和 FUS 基因存在突变，而 10 例患者携带 C9orf72 扩增。一位女性患者携带了 MAPT 基因中的 D348G 突变，该突变先前在一个意大利家族性下运动神经元疾病患者中报道过。我们的患者同时存在上下运动神经元的体征，早期出现呼吸困难，出现静止性和运动性震颤，疾病进展缓慢（>11 年）。本病例进一步扩展了与 MAPT 基因突变相关的临床表型，并提示尽管很少见，但 MAPT 突变可引起 ALS，因此应在 ALS 患者中进行分析，尤其是那些有早期呼吸困难和长期疾病的患者。
