Skeletal dysplasia

Gene: EXOC6B

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 (four unrelated cases and functional evidence) for the association of this gene with green rating on the next GMS update.

Created: 23 Oct 2024, 2:32 p.m. | Last Modified: 23 Oct 2024, 2:32 p.m.

Panel Version: 6.27

PMID:26669664 reported two brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones. They were identified with a homozygous nonsense variant in EXOC6B gene (p.Tyr302Ter).

PMID:30284759 reported two sisters with dislocations of the hips and knees, long slender fingers with distal tapering and significant motor disability but normal (older sister) or low-normal intelligence (younger sister). They were identified with a homozygous in-frame deletion of exons 9-20 in EXOC6B gene.

PMID:36150098 reported two unrelated individuals with the same condition, Spondyloepimetaphyseal dysplasia with joint laxity, type 3. One of them was identified with a homozygous frameshift exon 20 deletion and the other with a homozygous nonsense variant (p.Leu134Ter). Functional studies on patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis.

This gene has been associated with relevant phenotypes in OMIM (MIM #618395), but not yet in Gene2Phenotype.
Sources: Literature

Created: 23 Oct 2024, 2:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondyloepimetaphyseal dysplasia with joint laxity, type 3, OMIM:618395

Publications

• 26669664
• 30284759
• 36150098