Oswaldo Cruz University Hospital, Universidade de Pernambuco, Recife, Brazil.
VIB-UAntwerp Center for Molecular Neurology, Antwerp, Belgium.
Mol Genet Genomic Med. 2021 Oct;9(10):e1783. doi: 10.1002/mgg3.1783. Epub 2021 Sep 25.
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.
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.
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.
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.
HINT1 基因隐性失活突变与以运动轴索性周围神经病伴肌强直为主要表现的神经病相关。全世界共报道了 24 种不同的致病性变异，包括欧洲和亚洲确认的 4 种创始变异。大多数患者携带古老的斯拉夫创始变异 c.110G>C（p.Arg37Pro），该变异在欧洲从东到西呈分布梯度。
我们报告了一例南美的 HINT1 神经病病例，该病例通过对神经病基因panel 的大规模平行测序确定。为了研究变异的起源，我们进行了单倍型分析。
一名巴西青少年出现不对称起病的隐性轴索性运动神经病，伴有肌束颤动。针电极肌电图发现肌强直。他的父母没有血缘关系，也没有欧洲血统。患者携带 HINT1 第一外显子的双等位基因致病性 p.Arg37Pro 改变。两个等位基因是同源的，起源于与欧洲报道的相同的祖先创始等位基因。
我们的发现将 HINT1 神经病的地理分布扩展到了南美洲，我们在一名无明显欧洲血统的巴西青少年中描述了一种公认的创始变异。我们证实了肌强直这一标志性特征与该疾病的关联。
