Severe microcephaly

Gene: WLS

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: 10 Oct 2023, 2:56 p.m. | Last Modified: 10 Oct 2023, 2:56 p.m.

Panel Version: 4.33

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: There are sufficient unrelated cases with different homozygous variants in this gene and a consistent phenotype to support a gene-disease association. Progressive microcephaly (head circumference, 2 to 5.9 SD below the mean) was seen in all affected patients for whom data were available. Therefore suggesting this gene is rated Green at the next GMS panel update.

Created: 9 May 2023, 2:11 p.m. | Last Modified: 9 May 2023, 2:15 p.m.

Panel Version: 4.9

Green List (high evidence)

- Homozygous variants in 10 affected persons from 5 unrelated families.
- Affected individuals had multiorgan defects, including microcephaly, facial dysmorphism, foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects.
- The mutations affected WLS protein stability and Wnt signaling. Knock-in mice showed tissue and cell vulnerability consistent with Wnt-signaling intensity and individual and collective functions of Wnts in embryogenesis.
Sources: Literature

Created: 11 Oct 2021, 7:28 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
structural congenital anomalies

Publications

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