Likely inborn error of metabolism

Gene: GMPPA

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval

Created: 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

Green List (high evidence)

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 list

Created: 22 Jul 2020, 8:22 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)

Publications

• 24035193
• 28574218