Ketotic hypoglycaemia
Gene: MCEE
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment when marking as ready: Confirmed that mode of inheritance should remain biallelic, despite PMID: 17823972 reporting two cell lines from patients as heterozygous, as the vast majority of reports say homozygous, as well as Gene2Phenotype, OMIM, UKGTN and Illumina sources.Created: 14 Jun 2016, 8:07 a.m.
Comment on list classification: Gene added by reviewer and rated as green for inclusion on this panel. It is a confirmed DD gene for Methylmalonyl-CoA epimerase deficiency, and more than 3 family reports have now been published, though it seems to be a rare cause of methylmalonyl-CoA epimerase deficiency and patients may have mild symptoms. Two cases in where the patient were also homozygous for variants in another gene in the pathway.Created: 8 Jun 2016, 1:01 p.m.
Comment on mode of inheritance: Mode of inheritance confirmed in OMIM and G2P, and review.Created: 20 Apr 2016, 1:25 p.m.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for gene MCEE were set to metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections; Methylmalonyl-CoA epimerase deficiency
MCEE was added to Ketotic hypoglycaemiapanel. Sources: UKGTN,Illumina TruGenome Clinical Sequencing Services,Expert Review,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
Publications for MCEE were set to 16697227 - proband and sibling with mild methylmalonic aciduria were found to be homozygous for the c.139C>T, p.R47X variant, with heterozygous unaffected parents; 16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene); 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972 - sequencing of cell lines from 229 patients with elevations of methylmalonic acid excretion for which no cause was known identified 5 cell lines with MCEE variants. In fibroblast lines from two patients with the c.139C>T, p.R47X variant, WT cDNA corrected the biochemical phenotype in the cells.
Publications for MCEE were set to 16697227 - proband and sibling with mild methylmalonic aciduria were found to be homozygous for the c.139C>T, p.R47X variant, with heterozygous unaffected parents; 16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene); 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972 - sequencing of 229 patients with elevations of methylmalonic acid excretion for which no cause was known identified 5 patients with MCEE variants. In fibroblast lines from two patients with the c.139C>T, p.R47X variant, WT cDNA corrected the biochemical phenotype in the cells.
Publications for MCEE were set to 16697227; 16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene); 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972 - sequencing of 229 patients with elevations of methylmalonic acid excretion for which no cause was known identified 5 patients with MCEE variants. In fibroblast lines from two patients with the c.139C>T, p.R47X variant, WT cDNA corrected the biochemical phenotype in the cells.
This gene has been classified as Amber List (Moderate Evidence).
Publications for MCEE were set to 16697227; 16752391 (a case report of a patient who was homozygous for the R47X variant in MCEE, but also homozygous for a second variant in the SPR gene); 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972
This gene has been classified as Green List (High Evidence).
Publications for MCEE were set to 16697227; 16752391; 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972
Publications for MCEE were set to PMID: 16697227; 16752391; 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972
Publications for MCEE were set to PMID: 16697227; 16752391; 25763508 (a case homozygous for c.139C>T, p.Arg47* in the MCEE gene, and c.751A>T, p.Lys251* in the SRD gene; 17823972
Phenotypes for MCEE were set to metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections; Methylmalonyl-CoA epimerase deficiency
Mode of inheritance for MCEE was changed to BIALLELIC, autosomal or pseudoautosomal
This gene has been classified as Amber List (Moderate Evidence).
MCEE was added to Ketotic hypoglycaemiapanel. Sources: Literature