Skeletal dysplasia

Gene: PLCB3

Red List (low evidence)

Comment on list classification: Promoting from grey to red. 1 case reported and some functional data showing the effect on protein levels of the variant found.

Created: 20 Jan 2021, 8:56 p.m. | Last Modified: 20 Jan 2021, 8:56 p.m.

Panel Version: 2.63

Associated with Spondylometaphyseal dysplasia with corneal dystrophy#618961 (AR) in OMIM.

As reviewer notes, PMID: 29122926 - Ben-Salem et al 2018 - report a consanguineous extended family from UAE with 2 children (cousins) with a new autosomal recessive spondylometaphyseal dysplasia (SMD) associated with intellectual disability and corneal dystrophy (SMDCD) caused by a homozygous variant in PLCB3, c.2632G>T, p.A878S. The variant was identified by homozygosity mapping and then exome sequencing. Heterozygous carriers were healthy. The PLCB3 c.2632G>T  variant was not present in 200 healthy chromosomes from the same ethnic background, and it was not listed in dbSNP databases nor in EVS. It has been reported in the heterozygous state with an MAF of 1.824e-05 in ExAC. Functional studies showed that the p.A878S is a hypomorphic variant that appears to decrease PLCB3 levels in the cell, which leads to an increase in the level of its substrate PIP(2) in the cell.

Created: 20 Jan 2021, 8:55 p.m. | Last Modified: 20 Jan 2021, 8:55 p.m.

Panel Version: 2.62

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaphyseal dysplasia with corneal dystrophy OMIM:618961; spondylometaphyseal dysplasia with corneal dystrophy MONDO:0030074

Publications

• 29122926

Red List (low evidence)

Single consanguineous family reported.
Sources: Literature

Created: 3 Aug 2020, 10:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaphyseal dysplasia with corneal dystrophy, MIM# 618961

Publications

• 29122926