Severe microcephaly

Gene: LRRC8C

I don't know

Comment on publications: PMID:39623139 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 25 Mar 2025, 9:39 a.m. | Last Modified: 25 Mar 2025, 9:39 a.m.

Panel Version: 7.21

PMID:39623139 reported two unrelated individuals with a multisystem disorder characterised by considerable phenotypic variability, but with overlapping features including telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature.

One patient had a 1-bp heterozygous insertion (p.(Leu400IlefsTer8)) in LRRC8C gene, while the other one had a heterozygous missense variant in the same gene (p.(Val390Leu)). There is also evidence from in vitro functional assay available. The evidence also suggests that both variants result in gain-of-function effect.

`This gene has been associated with relevant phenotype in OMIM (MIM #621056), but not yet in Gene2Phenotype.
Sources: Literature

Created: 24 Mar 2025, 9:48 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
TIMES syndrome, OMIM:621056

Publications

• 39623139

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments