Amyotrophic lateral sclerosis/motor neuron disease
Gene: SIGMAR1Comment when marking as ready: Reported in one family with juvenile ALS and two families with ALS +/- fronto temporal dementiaCreated: 19 Dec 2016, 3:34 p.m.
Comment on publications: 27821430Created: 19 Dec 2016, 3:31 p.m.
Comment on list classification: Is green on the Charcot-Marie Tooth disease version 1.1 panel.Created: 3 Nov 2016, 7:04 p.m.
Promoted to version 1 on 19th December 2016 following external review and internal curation
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.
This gene has been classified as Green List (High Evidence).
Mode of inheritance for SIGMAR1 was changed to BIALLELIC, autosomal or pseudoautosomal
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 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.
SIGMAR1 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen
SIGMAR1 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Sources: Radboud University Medical Center, Nijmegen