Skeletal dysplasia

Gene: BGN

Green List (high evidence)

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

Created: 24 Feb 2025, 6:08 p.m. | Last Modified: 24 Feb 2025, 6:08 p.m.

Panel Version: 7.23

Comment on list classification: There is sufficient evidence available for the association of this gene with green rating on the next GMS update.

Created: 23 Oct 2024, 1:20 p.m. | Last Modified: 23 Oct 2024, 1:20 p.m.

Panel Version: 6.25

As reviewed by Tracy Lester, PMID:27236923 reported three unrelated families with BGN variants and presenting with X-Linked Spondyloepimetaphyseal Dysplasia (SEMD).

This gene has been associated with relevant phenotypes in both OMIM (MIM #300106) and Gene2Phenotype (with 'strong' rating on the DD panel).

Created: 23 Oct 2024, 1:18 p.m. | Last Modified: 23 Oct 2024, 1:18 p.m.

Panel Version: 6.23

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Spondyloepimetaphyseal dysplasia, X-linked, OMIM:300106

Publications

• 27236923

Green List (high evidence)

Cho et al report on finding missense variants in 3 families with SEMD segregating in an XLR pattern.
'Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-β) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-β. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define “XLR SEMD, BGN type” as a nosologic entity.'
Sources: NHS GMS

Created: 18 Oct 2024, 9:28 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Skeletal dysplasia; Spondyloepimetaphyseal dysplasia

Publications

• 27236923