Pasutharnchat Nath, Taychargumpoo Chamaiporn, Amornvit Jakkrit, Sombuntham Premsuda, Sirichana Worawan
Division of Neurology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Division of Neurology, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Neurol Sci. 2025 Feb;46(2):935-941. doi: 10.1007/s10072-024-07801-4. Epub 2024 Oct 12.
Mutations in the Dynactin 1 (DCTN1) gene lead to various neurodegenerative disorders. The p.Gly59Ser mutation, the first pathogenic mutation identified in DCTN1, was initially reported in a family with distal hereditary motor neuropathy and early vocal cord paralysis. Since its discovery in 2003, this mutation has been documented in only three families worldwide, to the best of our knowledge.
This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review.
Five of the patients were female. The mean age of onset was 32.6 ± 1.9 years. Thai patients showed early involvement of intrinsic hand, facial, and bulbar muscles, with vocal cord impairment manifesting later in the disease course. Tongue fasciculations, not previously reported with this mutation, were observed in most Thai patients. Bilateral split-hands were consistently noted. Arytenoidectomy and cordotomy have proven beneficial in relieving upper airway obstruction and preventing life-threatening upper airway complications from vocal cord paralysis.
The p.Gly59Ser mutation in DCTN1 presents with autosomal-dominant, adult-onset, lower motor neuronopathy/neuropathy. Compared to earlier reports, Thai patients exhibited more widespread involvement, including facial, bulbar, tongue, vocal cord, and limb muscles. In addition to vocal cord paralysis, the split-hand phenomenon emerges as another clinical hallmark of this condition.
动力蛋白激活蛋白1（DCTN1）基因突变会导致多种神经退行性疾病。p.Gly59Ser突变是在DCTN1中鉴定出的首个致病突变，最初在一个患有远端遗传性运动神经病和早期声带麻痹的家族中被报道。据我们所知，自2003年发现该突变以来，全球仅在三个家族中记录到这种突变。
本研究对来自一个携带DCTN1基因p.Gly59Ser突变的泰国家族的6名患者进行了检查，并进行了文献综述。
5名患者为女性。平均发病年龄为32.6±1.9岁。泰国患者早期累及手部固有肌、面部肌肉和延髓肌，声带损害在病程后期出现。大多数泰国患者观察到舌肌束颤，此前该突变未报告有此症状。双侧裂手畸形持续存在。已证实杓状软骨切除术和声带切开术有助于缓解上呼吸道梗阻，并预防声带麻痹引起的危及生命的上呼吸道并发症。
DCTN1基因中的p.Gly59Ser突变表现为常染色体显性遗传、成人发病的下运动神经元病/神经病。与早期报告相比，泰国患者受累范围更广，包括面部、延髓、舌、声带和肢体肌肉。除声带麻痹外，裂手现象是这种疾病的另一个临床特征。
