Clefting

Gene: PGAP3

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 2 May 2024, noon | Last Modified: 2 May 2024, noon

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Comment on list classification: There is sufficient evidence (>10 unrelated cases) available for promoting this gene to green rating in the next GMS review.

Created: 19 Jun 2023, 6:14 p.m. | Last Modified: 19 Jun 2023, 6:14 p.m.

Panel Version: 4.35

PMID:28390064 - 10 patients from eight families presented with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Nine patients from seven families were homozygous for the same variant (c.402dupC/ p.M135Hfs*28), while one patient had a different homozygous variant ( c.817_820delGACT/ p.D273Sfs*37). Of nine patients with p.M135Hfs*28 variant, eight patients from seven families (except one of the two patients from family 7) had cleft palate. But, the only patient with the different variant did not have cleft palate.

DECIPHER database - Of seven patients reported with biallelic sequence variants, three patents with homozygous variants were reported with cleft palate and two patients with compound heterozygous variants were reported with cleft soft palate (PMID:37010288).

OMIM associated patients with autosomal recessive variants in PGAP3 to hyperphosphatasia with impaired intellectual development syndrome 4 (MIM #615716) and cleft palate has been recorded as one of the clinical manifestations occurring in some patients.
Sources: Literature

Created: 19 Jun 2023, 6:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperphosphatasia with impaired intellectual development syndrome 4, OMIM:615716

Publications

• 28390064
• 37010288