Genetic and Clinical Features of 10 Families With Hereditary Sensory Neuropathies.

Objective: Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families.

Methods: Clinical data from 10 families with HSNs were collected retrospectively. Genetic screening was performed by whole exome sequencing (WES). Repeated-primed PCR and capillary electrophoresis were performed for WES-negative patients to analyze repeat expansions in RFC1.

Results: Among the 10 probands with HSNs, eight cases were sporadic, and two had a positive family history. Six probands had early-onset (onset age < 20 years). Seven probands presented with pure-HSNs type, and three exhibited HSNs-complex type with ataxia. Variants in the NTRK1, SPTLC1, COX20, PUM1, and RFC1 genes were detected in six probands. A novel variant, c.444C>A (p.N148K), in NTRK1 was identified in an autosomal recessive inheritance family with HSAN-IV, and a novel variant, c.182dup (p.H61Qfs*31), in PUM1 was identified in a proband with adult-onset paresthesia and mild cerebellar ataxia. Additionally, biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in the RFC1 gene was identified in a proband with sensory neuropathy, ataxia, and right vestibular hypofunction.

Conclusions: The novel variants in NTRK1 and PUM1 expanded the genotypic spectrum of HSNs. This study highlights the associations between sensory neuropathies and other symptoms, particularly cerebellar ataxia. Given the ultra-rarity of HSNs, future multicenter studies with larger cohorts may facilitate the identification of novel variants, improve genetic diagnostic rates, and enhance disease recognition.