Congenital myaesthenic syndrome
Gene: GFPT1Comment on phenotypes: Previous phenotypes:
Congenital Myasthenic Syndrome, Recessive;Myasthenia, congenital, 12, with tubular aggregates, 610542;Limb-girdle congenital myasthenic syndrome;tubular aggregatesCreated: 22 Mar 2021, 1:46 p.m. | Last Modified: 22 Mar 2021, 1:46 p.m.
Panel Version: 2.24
PMID:21975507;In 13 unrelated families with autosomal recessive congenital myasthenic syndrome-12 (CMS12, OMIM:610542), Senderek et al. (2011, PMID:21310273) identified 18 different mutations in the GFPT1 gene. All mutations were homozygous or compound heterozygous.Created: 10 May 2019, 11:09 a.m.
Review and rating from Michael Oldridge (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust), submitted by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 30 Apr 2019, 9:30 a.m.
see PanelAppCreated: 29 Apr 2019, 4:33 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital Myasthenic Syndrome, Recessive; Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; tubular aggregates
When mutations in GFPT1 were first identified as a cause of CMS, a number of patients (were found to have the transversion c.22C>A in the 3'-UTR of the gene. IN all four cases, the mutation was found compound heterozygous to a missense or protein-truncating mutation. This variant creates a microRNA binding site, and binding of microRNA206 reduced GFPT1 expression [Dusl et al., 2015 PMID:25765662]. Dusl et al., propose that variants in the 3'UTR should therefore be considered during genetic testing.Created: 2 Feb 2017, 2:49 p.m.
Comment when marking as ready: Green review plus >3 cases of GFPT1 mutations causing Congenital Myasthenic Syndrome (OMIM:610542) plus zebrafish animal model.Created: 26 Jan 2017, 5:04 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.Created: 26 Jan 2017, 4:57 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Limb-girdle congenital myasthenic syndrome; tubular aggregates
Publications
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: GFPT1 were changed from Congenital Myasthenic Syndrome, Recessive; Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; tubular aggregates to Myasthenia, congenital, 12, with tubular aggregates, OMIM:610542
Publications for gene: GFPT1 were set to 21975507; In 13 unrelated families with autosomal recessive congenital myasthenic syndrome-12 (CMS12, OMIM:610542), Senderek et al. (2011, PMID:21310273) identified 18 different mutations in the GFPT1 gene. All mutations were homozygous or compound heterozygous; 22230109; 23569079
Source NHS GMS was added to GFPT1.
Source Wessex and West Midlands GLH was added to GFPT1. Rating Changed from Green List (high evidence) to Green List (high evidence)
22 February 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Green List (High Evidence).
Publications for GFPT1 were set to 21975507; In 13 unrelated families with autosomal recessive congenital myasthenic syndrome-12 (CMS12, OMIM:610542), Senderek et al. (2011, PMID:21310273) identified 18 different mutations in the GFPT1 gene. All mutations were homozygous or compound heterozygous; 22230109; 23569079
Publications for GFPT1 were set to 21975507; 21310273; 22230109; 23569079
Publications for GFPT1 were set to 21975507; 21310273; 22230109; 23569079;
Mode of inheritance for GFPT1 was changed to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for GFPT1 were set to Congenital Myasthenic Syndrome, Recessive; Myasthenia, congenital, 12, with tubular aggregates, 610542; Limb-girdle congenital myasthenic syndrome; tubular aggregates
GFPT1 was added to Congenital myaestheniapanel. Sources: Radboud University Medical Center, Nijmegen
GFPT1 was added to Congenital myaestheniapanel. Sources: UKGTN
GFPT1 was added to Congenital myaestheniapanel. Sources: Illumina TruGenome Clinical Sequencing Services