Undiagnosed metabolic disordersGene: ALG14
There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 9 Jul 2020, 12:13 p.m. | Last Modified: 9 Jul 2020, 12:13 p.m.
Panel Version: 1.418
Comment on list classification: Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous (p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient.
Created: 9 Jul 2020, 12:11 p.m. | Last Modified: 9 Jul 2020, 12:11 p.m.
Panel Version: 1.417
Associated with phenotype in OMIM, not in G2P / DD. At least 2 variants reported in 2 sisters
Created: 23 Feb 2017, 5:11 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
?Myasthenic syndrome, congenital, 15, without tubular aggregates 616227
Gene: alg14 has been classified as Green List (High Evidence).
Tag for-review was removed from gene: ALG14.
Tag for-review tag was added to gene: ALG14.
Publications for gene: ALG14 were set to 27604308
Gene: alg14 has been classified as Amber List (Moderate Evidence).
Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added
ALG14 was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Red Model of inheritance for gene ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
ALG14 was added to Undiagnosed metabolic disorderspanel. Sources: Literature
ALG14 was created by sleigh