Likely inborn error of metabolism - targeted testing not possible
Gene: GMPPA
The rating of this gene has been updated following NHS Genomic Medicine Service approvalCreated: 3 Mar 2022, 12:59 p.m. | Last Modified: 3 Mar 2022, 12:59 p.m.
Panel Version: 2.223
Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in unrelated cases.Created: 14 Jan 2021, 10:56 a.m. | Last Modified: 14 Jan 2021, 10:56 a.m.
Panel Version: 2.24
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 14 Jan 2021, 10:49 a.m. | Last Modified: 14 Jan 2021, 10:49 a.m.
Panel Version: 2.24
Phenotypes
Alacrima, achalasia, and mental retardation syndrome OMIM:615510
Variants in this gene induce a significant GDP-mannose overload, which is postulated to affect protein glycosylation.
PMID: 24035193;
- 13 affecteds from 9 families
- GDP-mannose levels were shown to be increased in 2 of the affecteds
PMID: 28574218;
- 2 sisters with achalasia, alacrima, hypohydrosis, apparent intellectual disability, seizures, microcephaly, esotropia, and craniofacial dysmorphism homozygous for c.853+1G>A.
- Loss of GMPPA protein leading to increased levels of GDP-mannose were demonstrated
Sources: Expert listCreated: 22 Jul 2020, 8:22 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Publications
Tag for-review was removed from gene: GMPPA.
Source Expert Review Green was added to GMPPA. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: GMPPA was added gene: GMPPA was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list for-review tags were added to gene: GMPPA. Mode of inheritance for gene: GMPPA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GMPPA were set to 24035193; 28574218 Phenotypes for gene: GMPPA were set to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)