Cytopenias and congenital anaemias

Gene: GCLC

Green List (high evidence)

Comment on list classification: changed status from Red to Green due to evidence found in the literature

Created: 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 disorder

Created: 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

• 10733484
• 12663448
• 18024385

Red List (low evidence)

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

• 10515893

Green List (high evidence)

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