Skeletal dysplasia

Gene: WBP11

Green List (high evidence)

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

Created: 6 Mar 2022, 6:30 p.m. | Last Modified: 6 Mar 2022, 6:30 p.m.

Panel Version: 2.184

Comment on list classification: Promoting from red to amber with recommendation for a green rating following GMS review.

Created: 11 Feb 2021, 8:32 p.m. | Last Modified: 11 Feb 2021, 8:32 p.m.

Panel Version: 2.83

PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.

Vertebral anomalies were noted in 6/13 patients from 5 families. One patient had congenital scoliosis and one abnormalities of the right upper ribs. Genomics England clinical team suggest it just meets the threshold for the skeletal dysplasia panel.
Sources: Literature

Created: 11 Feb 2021, 8:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems

Publications

• 33276377