Skeletal dysplasia

Gene: SH3BP2

Green List (high evidence)

Cherubism is characterized by a loss of bone, restricted to the jaws, and by the replacement of this bone with fibrous tissues, leading to facial swelling. Involvement of the infraorbital rim and the orbital floor leads to the upward tilting of the eyeballs and consequent exposure of the inferior part of the sclerae, giving a 'cherubic' appearance. Submandibular lymph node enlargement is often reported. Functional impairment includes mastication and speech problems, tooth alterations, and loss of normal vision. Onset of the disease is usually between 14 months and 4 years of age. The disease progresses through puberty, then stabilizes, and in some cases regresses without treatment

Created: 24 Apr 2022, 1:20 a.m. | Last Modified: 24 Apr 2022, 1:20 a.m.

Panel Version: 0.163

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cherubism, MIM#118400

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Well described gene-disease association
Gain-of-function mechanism (mouse model demonstrated uncoupling from Tankyrase-mediatied destruction, which lead to hyperactivation of signalling pathways PMID: 22153076)
Pathogenic variants occur in exon 9, between within a 6 -amino acid sequence located between SH2 domain and the SH3-binding domain.
Full gene deletions do not lead to cherubism, therefore haploinsufficiency is not a disease mechanism.

Created: 20 Apr 2022, 1:34 a.m. | Last Modified: 20 Apr 2022, 1:34 a.m.

Panel Version: 0.163

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

Phenotypes
Cherubism, MIM#118400

Publications

• 11381256
• 22640988
• 20301316
• 22153076