Expanding the phenotype associated with biallelic WDR60 mutations: Siblings with retinal degeneration and polydactyly lacking other features of short rib thoracic dystrophies

Am J Med Genet A. 2018 Feb;176(2):438-442. doi: 10.1002/ajmg.a.38562. Epub 2017 Dec 22.


Ciliopathies are disorders of the primary cilium that can affect almost all organs and that are characterized by pleiotropy and extensive intra- and interfamilial phenotypic variability. Accordingly, mutations in the same gene can cause different ciliopathy phenotypes of varying severity. WDR60 encodes a protein thought to play a role in the primary cilium's intraflagellar transport machinery. Mutations in this gene are a rare cause of Jeune asphyxiating thoracic dystrophy (JATD) and short-rib polydactyly syndrome (SRPS). Here we report on a milder and distinct phenotype in a 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. Our finding broadens the spectrum of WDR60-related phenotypes and shows the utility of broad multigene panels during the genetic work-up of patients with ciliopathies.

Keywords: Bardet-Biedl syndrome; WDR60; ciliopathy.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adolescent
  • Adult
  • Cilia / genetics
  • Cilia / pathology
  • Ciliopathies / genetics
  • Ciliopathies / physiopathology
  • Ellis-Van Creveld Syndrome / genetics
  • Ellis-Van Creveld Syndrome / physiopathology
  • Exome / genetics
  • Female
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Polydactyly* / genetics
  • Polydactyly* / physiopathology
  • Retinal Degeneration* / genetics
  • Retinal Degeneration* / physiopathology
  • Ribs / physiopathology
  • Short Rib-Polydactyly Syndrome* / genetics
  • Short Rib-Polydactyly Syndrome* / physiopathology
  • Siblings
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • DYNC2I1 protein, human

Supplementary concepts

  • Jeune syndrome