Hereditary neuropathy or pain disorder
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.
gene: SIGMAR1 was added gene: SIGMAR1 was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH,Expert Review,Expert Review Green Mode of inheritance for gene: SIGMAR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SIGMAR1 were set to 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; PubMed: 21842496 - E102Q variant identified in a Saudi Arabian family to be associated with amyotrophic lateral sclerosis 16, juvenile; 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.; 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