Clefting

Gene: SF3B2

Green List (high evidence)

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

Created: 1 Feb 2023, 5:13 p.m. | Last Modified: 1 Feb 2023, 5:13 p.m.

Panel Version: 3.5

Comment on list classification: Promoting from grey to amber but with a green recommendation following GMS review. 4 families reported in which lateral oral clefting is part of the phenotype. Supportive Xenopus data.

Created: 10 Oct 2021, 12:51 p.m. | Last Modified: 10 Oct 2021, 12:51 p.m.

Panel Version: 2.51

As the expert reviewer Zornitza Stark comments PMID:34344887 (Timberlake et al 2021) reports seven kindreds with LOF variants in SF3B2 and a craniofacial microsomia phenotype in 22 affected individuals. Lateral oral cleft was recorded in 5 individuals (1 mild) from 4 families.

Created: 10 Oct 2021, 12:49 p.m. | Last Modified: 10 Oct 2021, 12:49 p.m.

Panel Version: 2.50

Green List (high evidence)

Twenty individuals from seven families reported with de novo or transmitted haploinsufficient variants in SF3B2. Affected individuals had mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities.

Targeted morpholino knockdown of SF3B2 in Xenopus resulted in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.

The families were ascertained from a cohort and the authors suggest that haploinsufficient variants in SF3B2 are the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.
Sources: Literature

Created: 7 Aug 2021, 7:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Craniofacial microsomia

Publications

• 34344887

Variants in this GENE are reported as part of current diagnostic practice