Clinical and neurophysiological characterization of p.Gly95Ser mutation in DCTN1: a study in a Thai family and a brief review

Abstract

Introduction: 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. Methods: This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review. Results: 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. Conclusions: 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.