Osteogenesis imperfecta

Gene: WNT11

Green List (high evidence)

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

Created: 6 Dec 2024, 12:14 p.m. | Last Modified: 6 Dec 2024, 12:14 p.m.

Panel Version: 4.9

Comment on gene classification: The rating of this gene can be added as green as this gene has been implicated in early-onset osteoporosis from three unrelated cases and was supported by evidence from functional studies. All three patients harboured heterozygous variants in WNT11 gene.

Three unrelated cases are reported in PMID: 34875064. A four year-old boy harbouring de novo heterozygous loss-of-function variant c.677_678dupGG (p.Leu227Glyfs*22) was reported with low BMD, osteopenia and several fractures.

A 51 year-old woman and her 69 year-old mother were identified with a heterozygous missense variant c.217G>A (p.Ala73Thr). The woman was reported with bone fragility, several fractures, osteoarthritis and osteoporosis, while her mother also had several osteoporotic fractures.

A 61 year-old woman that was reported with lumbar spine osteoarthritis had several fractures since 55 years of age was identified with a heterozygous missense variant c.865G>A (p.Val289Met).

This was also supported by results from functional studies, where cell lines with the loss-of-function variant generated by CRISPR-Cas9 showed reduced cell proliferation and osteoblast differentiation in comparison to wild-type. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells.

This gene has not yet been reported with any phenotypes either in OMIM or in G2P.
Sources: Literature

Created: 15 Feb 2023, 6:02 a.m. | Last Modified: 15 Feb 2023, 6:09 a.m.

Panel Version: 3.7

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

Phenotypes
osteoporosis, MONDO:0005298; osteoarthritis, MONDO:0005178; recurrent fractures

Publications

• 34875064