Rare multisystem ciliopathy disorders

Gene: WDR60

Added new-gene-name tag, new approved HGNC gene symbol for WDR60 is DYNC2I1

Created: 7 May 2020, 11:08 a.m. | Last Modified: 7 May 2020, 11:08 a.m.

Panel Version: 1.124

Comment on list classification: More than 3 unrelated cases now reported

Created: 18 Jun 2019, 3:41 p.m.

This gene is associated with Short-rib thoracic dysplasia 8 with or without polydactyly (#615503) only. In Gene2Phenotype it is associated with JEUNE SYNDROMES (confirmed) and SHORT-RIB POLYDACTYLY (confirmed)

PMID: 23910462 - McInerney-Leo et al 2013 - 2 cases. One in an Australian family with individual with SRPS type III. proband and one other family member affected. They detected two novel heterozygous mutations in WDR60, both were predicted to have a damaging effect on the protein. The mutations segregated appropriately in the unaffected parents and another affected family member. Second cases is of compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation.

PMID: 25492405 - McInerney-Leo et al 2015 - whole exome sequencing of 11 probands with Short-rib thoracic dystrophies and their parents and siblings. A homozygous variant (c.1924CT p.Arg642*) in WDR60 was found in individual SKDP‐144.3. This paper also reports the previously found compound heterozygous variants in individual SKDP‐42.3 (from McInerney-Leo et al 2013).

PMID: 26874042 - Cossu et al 2016 - in a Sardinian family with Jeune syndrome, they identified a homozygous single nucleotide variation (c.2840 A > T, p.Gln947Leu; NM_018051.4) in the WDR60 gene, for which both parents and the unaffected brother resulted heterozygous. The patient of 23 years had a relatively mild phenotype. This variation has been predicted as “possibly damaging” by Polyphen-2 (0.863), as “damaging” by SIFT and as “disease causing” by Mutation Taster.

PMID: 29271569 - Kakar et al 2018 - consanguineous Pakistani pedigree with two adolescent sisters affected by retinal degeneration and postaxial polydactyly, but lack of any further skeletal or chondrodysplasia features. By targeted high-throughput sequencing of genes known or suspected to be involved in ciliogenesis, we detected a novel homozygous N-terminal truncating WDR60 mutation (c.44delC/p.Ala15Glufs*90) that co-segregated with the disease in the family.

Summary - 5 unrelated cases now reported.

Created: 18 Jun 2019, 3:41 p.m.

Green List (high evidence)

Please note these additional publications each describing additional patients with bi-allelic variants and ciliopathy disorders.

Created: 7 Aug 2018, 5:21 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29271569, 26874042, 25492405

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

Red List (low evidence)

Only two reported cases -one familial and one single case

Created: 23 Jan 2017, 11:59 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia 8 with or without polydactyly 615503

Publications

• 23910462