Cytopenias and congenital anaemias
Gene: GCLC
Comment on list classification: changed status from Red to Green due to evidence found in the literatureCreated: 13 Mar 2017, 4:26 p.m.
Change status from Red to Green as there are more than three unrelated cases where Hereditary deficiency of gamma-GCS has been reported (associated with low erythrocyte levels of gamma-GCS and GSH leading to hemolytic anemia), see details supplied in publication section
Created: 13 Mar 2017, 4:25 p.m.
Comment on publications: Hereditary deficiency of gamma-GCS has been reported in a small number of patients and is associated with low erythrocyte levels of gamma-GCS and GSH leading to hemolytic anemia, the presence of neurological symptoms has also been reported.
The disorder to date has been detected in nine patients from seven families worldwide, recent examples include:
Mañú Pereira et al 2007 (PMID: 18024385) 1 affected (Moroccan origin) a single C>T transversion at cDNA nucleotide 1241 in the γ-GCS gene, this was the fourth case of GCS deficiency described in which chronic anaemia is associated with both severe neuropathy and mental retardation.
Hamilton et al 2003 (PMID: 12663448) two affected (1 family) reported a novel gamma-GCSH mutation, isolated from the cDNA of 2 related patients diagnosed with gamma-GCS deficiency. Each was found to be homozygous for a C>T missense mutation at nucleotide 379, encoding for a predicted Arg127Cys amino acid change.
Ristoff et al 2000 (PMID:10733484) reported 1 affected (large consanguineous Dutch family)
Beutler et al 1999 (PMID: 10515893) reported 1 affected
Hirono et all 1996 (PMID: 8634459) reported 3 unrelated Japanese patients
Created: 13 Mar 2017, 4:22 p.m.
Comment on phenotypes: included synonym for the disorderCreated: 13 Mar 2017, 2:58 p.m.
Added publications that give evidence of unrelated cases with Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, to support the status of the gene changing from Red to Green.Created: 13 Mar 2017, 2:27 p.m.
Publications
Comment when marking as ready: One case identified in the literature - insufficient evidence.Created: 2 Mar 2017, 9:51 a.m.
Only one case reported to date. Insufficient evidence.Created: 2 Mar 2017, 9:49 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency 230450
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Enzyme Disorder; Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency
Variants in this GENE are reported as part of current diagnostic practice
This gene has been classified as Green List (High Evidence).
Publications for GCLC were set to 10515893; 10733484; 12663448; 18024385; 8634459
Phenotypes for GCLC were set to Enzyme Disorder; Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency, 230450;Glutamate-cysteine ligase deficiency
Publications for GCLC were set to 10515893;10733484; 12663448; 18024385
Phenotypes for GCLC were set to Enzyme Disorder;Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency 230450
Promoted to V1 on 11 March 2017, after internal review and discussion with the clinical team.
This gene has been classified as Red List (Low Evidence).
Phenotypes for GCLC were set to Hemolytic anemia due to gamma-glutamylcysteine synthetase deficiency 230450
Publications for GCLC were set to 10515893
Mode of inheritance for GCLC was changed to BIALLELIC, autosomal or pseudoautosomal
GCLC was added to Cytopaenias and congenital anaemiaspanel. Sources: Radboud University Medical Center, Nijmegen
GCLC was created by LouiseD