A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation.
Alanine
/ genetics
Amyotrophic Lateral Sclerosis
/ diagnosis
Aspartic Acid
/ genetics
Cell Cycle Proteins
/ genetics
Female
Genetic Testing
/ methods
Genetic Variation
/ genetics
Glutamine
/ genetics
Heterozygote
High-Throughput Nucleotide Sequencing
/ methods
Humans
Male
Membrane Transport Proteins
/ genetics
Middle Aged
Mutation, Missense
/ genetics
Pedigree
Superoxide Dismutase-1
/ genetics
Valine
/ genetics
Familial ALS
Genetic counselling
Genetic variant of uncertain significance
OPTN
SOD1
Journal
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
ISSN: 1532-2653
Titre abrégé: J Clin Neurosci
Pays: Scotland
ID NLM: 9433352
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
10
01
2020
accepted:
20
03
2020
pubmed:
1
4
2020
medline:
30
9
2020
entrez:
1
4
2020
Statut:
ppublish
Résumé
About 10% of Amyotrophic Lateral Sclerosis (ALS) cases are familial (FALS), mainly related to mutations in C9ORF72, SOD1, TARDBP, and FUS genes. Recent data revealed the presence of multiple variants in ALS-associated genes in FALS in excess of what is to be expected by chance. FALS patients not carrying a pathogenic genetic mutation detected in their kindred have been reported. We report a FALS case, who did not carry the p.Ala5Val heterozygous SOD1 mutation that had been detected in other affected subjects of his kindred. He underwent Next-Generation Sequencing, revealing a novel p.Glu46Asp heterozygous OPTN variant of uncertain significance (VUS). Discordant genetic test results in FALS cases within the same family and the detection of variants of uncertain significance increase the complexities of genetic counselling.
Identifiants
pubmed: 32223976
pii: S0967-5868(20)30095-3
doi: 10.1016/j.jocn.2020.03.032
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
Membrane Transport Proteins
0
OPTN protein, human
0
SOD1 protein, human
0
Glutamine
0RH81L854J
Aspartic Acid
30KYC7MIAI
Superoxide Dismutase-1
EC 1.15.1.1
Valine
HG18B9YRS7
Alanine
OF5P57N2ZX
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
223-225Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.