Background: SH3TC2 variations lead to demyelinating recessive Charcot-Marie-Tooth (CMT) disease, which is commonly associated with early-onset scoliosis and cranial neuropathy. Data from Indian ethnicity is limited.
Objective: We aim to report the characteristics of patients with SH3TC2-associated neuropathy from an Indian cohort.
Patients and methods: Data of five unrelated subjects with SH3TC2 variations were analyzed.
Results: Clinical features included female predominance (n = 4), early-onset neuropathy (n = 2), pes cavus and hammer toes (n = 4), kyphoscoliosis (n = 1), impaired vision and hearing (n = 1), facial muscle weakness (n = 1), impaired kinaesthetic sense (n = 3), tremor (n = 2), and ataxia (n = 1). Four patients had the "CMT" phenotype, while one patient had Roussy-Levy syndrome. All had demyelinating electrophysiology with conduction velocities being "very slow" in one, "slow" in one, "mildly slow" in two, and "intermediate" in one patient. Brain stem auditory evoked potentials were universally abnormal though only one patient had symptomatic deafness. Seven variants were identified in SH3TC2 [homozygous = 3 (c.1412del, c.69del, c.3152G>A), heterozygous = 4 (c.1105C>T, c.3511C>T, c.2028G>C, c.254A>T)]. Except for c.3511C>T variant, the rest were novel. Three patients had additional variations in genes having pathobiological relevance in other CMTs or amyotrophic lateral sclerosis.
Conclusion: We provide data on a cohort of patients of Indian origin with SH3TC2 variations and highlight differences from other cohorts. Though the majority were not symptomatic for hearing impairment, evoked potentials disclosed abnormalities in all. Further studies are required to establish the functional consequences of novel variants and their interacting molecular partners identified in the present study to strengthen their association with the phenotype.
Keywords: Brainstem auditory evoked potentials; CMT4C; Charcot-Marie-Tooth diseases; SH3TC2-variation; deafness; genetic modifiers.