Rare multisystem ciliopathy disorders

Gene: C21orf2

Comment on list classification: Updated rating from Grey to Green: Two Green expert reviews, plus recent literature evidence for biallelic C21orf2 variants involved in Jeune syndrome (PMID:26167768).

Created: 16 Oct 2018, 2:46 p.m.

Comment on mode of inheritance: Biallelic MOI confirmed by OMIM and DD-G2P.

Created: 16 Oct 2018, 2:29 p.m.

Added new-gene-name tag: new approved HGNC gene symbol is CFAP410.

Created: 16 Oct 2018, 2:25 p.m.

Green List (high evidence)

C21ORF2 first reported as a cause of autosomal recessive cone-rod dystrophy (a homozygous
splicing mutation), but it was a single family (23105016). This gene was then identified as a cilial gene in a Nature Genetics paper (26167768), using a genome-wide siRNA knockdown strategy for ciliogenesis. Included within this paper were four families, all of whom had homozygous or compound heterozygous mutations and a spectrum of clinical phenotypes including retinal dystrophy with additional thoracic outlet features in some. Most recently another paper has described axial SMD in cases with mutations in this gene.

Created: 16 Sep 2018, 7:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Axial Spondylometaphyseal Dysplasia (axial SMD); Jeune Syndrome; Retinal Dystrophy

Publications

• 23105016
• 26167768
• 26974433

Green List (high evidence)

Multiple affected individuals from unrelated families reported with bi-allelic variants in this gene, associated with a skeletal/retinal phenotype consistent with a ciliopathy.

Created: 3 Aug 2018, 6:47 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylometaphyseal dysplasia, axial, MIM#602271

Publications

• 27548899, 26974433, 26167768

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