Hereditary neuropathy
Gene: SIGMAR1
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.Created: 9 May 2019, 5 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: This gene was added by a reviewer, and rated green by a second reviewer. There has been a commentary regarding whether SIGMARI variants are causal of motor neuron disease.Created: 9 May 2016, 8:46 a.m.
Source NHS GMS was added to SIGMAR1.
Source London North GLH was added to SIGMAR1. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile; PMID: 26088964 is a commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions. PMID: 26088963 - in reply, authors state that there is in vitro and in vivo evidence, and expression evidence, and that a case reported did not have the C9orf72 expansion; PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile. PMID: 26088964 is a commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions. PMID: 26088963 - in reply, authors state that there is in vitro and in vivo evidence, and expression evidence, and that a case reported did not have the C9orf72 expansion. PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.
This gene has been classified as Amber List (Moderate Evidence).
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile. PMID: 26088964 commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions; PMID: 26078401 - c.151+1G>T variant in SIGMARI resulted in a 60 bp deletion in the transcript, and segrated with the distal hereditary motor neuropathy in a Chinese family.
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis and c.672*31A>G (rs4879809) - the C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls; PMID: 26088964 commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic, and that previous reports of patients with SIGMARI variants were also shown to harbour C9orf72 expansions; PMID: 26078401 - 3 novel homozygous variants reported
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis; PMID: 26088964 commentary on PMID: 25678561 raising a lack of evidence for SIGMARI to be pathogenic...patients with SIGMARI variants were also shown to harbour C9orf72 expansions.
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis; PMID: 26088964 commentary raising the lack of evidence for SIGMARI to be pathogenic...patients with SIGMARI variants were also shown to harbour C9orf72 expansions.
Publications for SIGMAR1 were set to PMID: 26205306 one family report for association with Amyotrophic lateral sclerosis.
SIGMAR1 was created by MReilly-925
SIGMAR1 was added to Charcot-Marie-Tooth diseasepanel. Sources: Expert Review