Osteopetrosis

Gene: TGFB1

Green List (high evidence)

Established gene-disease association - CED is characterised by hyperostosis of the long bones and skull along with other phenotypes. Some individuals can present with osteosclerosis as well.

Mechanism of disease is GoF due to the disruption to dimerization of LAP and binding to active TGFB1, leading to increased active TGFB1 release from the cell.

PMID: 30034812 - 35F presenting with a range of features including hyperostosis of long bones of upper limbs. A missense mutation in TGFB1 was identified p.Arg218Cys (singleton gnomAD v4.1)

PMID: 39014191 - At least two individuals presenting with hyperostosis and a missense variant in TFGB1 which were confirmed de novo.
A third individual was identified with an inframe deletion in exon 1 of TGFB1 (c.112-120del) that resulted in an increase in TGFB1 activity.

Created: 3 Dec 2024, 3:59 a.m. | Last Modified: 3 Dec 2024, 3:59 a.m.

Panel Version: 0.34

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Camurati-Engelmann disease MONDO:0007542

Publications

• 20301335
• 30034812
• 39014191

Mode of pathogenicity
Other