HINT1 founder mutation causing axonal neuropathy with neuromyotonia in South America: A case report.
Charcot-Marie-Tooth disease
HINT1
founder effect
inherited peripheral neuropathy
neuromyotonia
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
18
05
2021
received:
10
03
2021
accepted:
02
08
2021
pubmed:
26
9
2021
medline:
23
3
2022
entrez:
25
9
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 34562060
doi: 10.1002/mgg3.1783
pmc: PMC8580089
doi:
Substances chimiques
HINT1 protein, human
0
Nerve Tissue Proteins
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1783Informations de copyright
© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
J Neurochem. 2017 Dec;143(5):507-522
pubmed: 28902413
Nat Genet. 2012 Oct;44(10):1080-3
pubmed: 22961002
Neuropediatrics. 2016 Apr;47(2):119-22
pubmed: 26760849
Neuromuscul Disord. 2018 Aug;28(8):646-651
pubmed: 30001929
Oncogene. 2006 Feb 2;25(5):713-21
pubmed: 16186798
Brain. 2017 Apr 1;140(4):868-877
pubmed: 28007994
Neurogenetics. 2015 Jan;16(1):43-54
pubmed: 25342199
Mol Genet Genomic Med. 2021 Oct;9(10):e1783
pubmed: 34562060
Neuromuscul Disord. 2019 Dec;29(12):979
pubmed: 31787464
Eur J Med Genet. 2019 Mar;62(3):190-194
pubmed: 30006059
J Neuropathol Exp Neurol. 2014 Jul;73(7):693-701
pubmed: 24918641
Handb Clin Neurol. 2018;148:653-665
pubmed: 29478606
J Biol Chem. 2006 Sep 15;281(37):27356-66
pubmed: 16835243
Curr Opin Neurol. 2017 Oct;30(5):471-480
pubmed: 28678038
Clin Neurol Neurosurg. 2016 Sep;148:85-7
pubmed: 27428488
Sci Rep. 2017 Feb 27;7:43468
pubmed: 28240305
Mol Biol Rep. 2020 Feb;47(2):1331-1337
pubmed: 31848916
Muscle Nerve. 2015 Dec;52(6):1110-3
pubmed: 26182879
Cell Cycle. 2012 Jun 1;11(11):2206-15
pubmed: 22647378