HINT1 Founder Mutation Causing Axonal Neuropathy with Neuromyotonia in South America: A Case Report

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2021 Sep 25

PMID 34562060

Citations 5

Authors

Bianca de Aguiar Coelho Silva Madeiro

Kristien Peeters

Elker Lene Santos de Lima

Silvia Amor-Barris

Els De Vriendt

Albena Jordanova

Maria Tereza Cartaxo Muniz

Carolina da Cunha Correia

Affiliations

Soon will be listed here.

Abstract

Background: Recessive loss-of-function mutations in HINT1 are associated with predominantly motor axonal peripheral neuropathy with neuromyotonia. Twenty-four distinct pathogenic variants are reported all over the world, including four confirmed founder variations in Europe and Asia. The majority of patients carry the ancient Slavic founder variant c.110G>C (p.Arg37Pro) that shows a distribution gradient from east to west throughout Europe.

Methods: We report a case of HINT1 neuropathy in South America, identified by massive parallel sequencing of a neuropathy gene panel. To investigate the origin of the variant, we performed haplotyping analysis.

Results: A Brazilian adolescent presented with recessive axonal motor neuropathy with asymmetric onset and fasciculations. Neuromyotonia was found on needle electromyography. His parents were not consanguineous and had no European ancestry. The patient carried biallelic pathogenic p.Arg37Pro alterations in the first exon of HINT1. Both alleles were identical by descent and originated from the same ancestral founder allele as reported in Europe.

Conclusion: Our findings expand the geographic distribution of HINT1 neuropathy to South America, where we describe a recognized founder variant in a Brazilian adolescent with no apparent European ancestry. We confirm the association of the hallmark sign of neuromyotonia with the disease.

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HINT1 founder mutation causing axonal neuropathy with neuromyotonia in South America: A case report.

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PMID: 34562060 PMC: 8580089. DOI: 10.1002/mgg3.1783.

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