Congenital myaesthenic syndrome
Gene: SLC18A3
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; ophthalmopleggia and apnea; Myasthenic syndrome, congenital, 21, presynaptic, 617239
Comment on list classification: Updated rating from Grey to Green: 1 green review from expert, plus 2 unrelated cases with addition of mouse model.Created: 7 Feb 2017, 4:23 p.m.
Mouse model: 2 mouse models of reduced SLC18A3 expression (knockout and knockdown) provide support for SLC18A3 as a genetic cause of presynaptic congenital myasthenic syndrome (PMID:16950158, PMID:24260111).Created: 7 Feb 2017, 4:18 p.m.
PMID:27590285 (O'Grady et al., 2016) identify biallelic variants in SLC18A3 in 2 unrelated individuals presenting with features seen in presynaptic congenital myasthenic syndrome. Patient 1 was born to unaffected nonconsanguineous Filipino parents and carries a deletion of CHAT and SLC18A3 on 1 allele, and a missense variant c.557 G>C; p.(Gly186Ala) in SLC18A3 on the second allele; his mother was heterozygous for Gly186Ala, and DNA from the father was unavailable.
Patient 2 was the only child of consanguineous East Turkish parents and carried a homozygous recessive missense variant, c.1192G>C, p.(Asp398His); both parents were heterozygous for the mutation.Created: 2 Feb 2017, 3:16 p.m.
Comment on mode of inheritance: Mode of inheritance supported by OMIM and PMID:27590285.Created: 2 Feb 2017, 3:10 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myasthenic syndrome; ophthalmopleggia and apnea
Publications
Phenotypes for gene: SLC18A3 were changed from Congenital myasthenic syndrome; ophthalmopleggia and apnea; Myasthenic syndrome, congenital, 21, presynaptic, 617239 to Myasthenic syndrome, congenital, 21, presynaptic, OMIM:617239
Publications for gene: SLC18A3 were set to PMID: 27590285
Source NHS GMS was added to SLC18A3.
Source Wessex and West Midlands GLH was added to SLC18A3. 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).
Mode of inheritance for SLC18A3 was changed to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for SLC18A3 were set to Congenital myasthenic syndrome; ophthalmopleggia and apnea; Myasthenic syndrome, congenital, 21, presynaptic, 617239
SLC18A3 was added to Congenital myaestheniapanel. Sources: Eligibility statement prior genetic testing
SLC18A3 was created by [email protected]