WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy

Am J Med Genet A. 2022 Oct;188(10):3071-3077. doi: 10.1002/ajmg.a.62903. Epub 2022 Jul 25.

Abstract

Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED. Here we describe a 4-year-old male CED patient whose features include dolichocephaly, multi-suture craniosynostosis, epicanthus, frontal bossing, narrow thorax, limb shortening, and brachydactyly. The patient presented early-onset chronic kidney disease and was transplanted at the age of 2 years and 5 months. At the age of 3.5 years a retinal degeneration was diagnosed. Targeted sequencing by NGS revealed the presence of compound heterozygous variants in the WDR35 gene. The variants are a novel missense change in exon 9 p.(Gly303Arg) and a previously described nonsense variant in exon 18 p.(Leu641*). Our findings suggest that patients with WDR35 defects may be at risk to develop early-onset retinal degeneration. Therefore, CED patients with pathogenic variation in this gene should be assessed at least once by the ophthalmologist before the age of 4 years to detect early signs of retinal degeneration.

Keywords: WDR35; ciliopathy; cranioectodermal dysplasia (Sensenbrenner syndrome); early-onset retinal dystrophy (EORD); end-stage renal disease (ESRD).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone and Bones / abnormalities
  • Child, Preschool
  • Craniosynostoses* / complications
  • Craniosynostoses* / diagnosis
  • Craniosynostoses* / genetics
  • Cytoskeletal Proteins / genetics
  • Dwarfism
  • Ectodermal Dysplasia
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kidney Failure, Chronic*
  • Male
  • Mutation
  • Osteochondrodysplasias
  • Retinal Dystrophies* / diagnosis
  • Retinal Dystrophies* / genetics

Substances

  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • WDR35 protein, human

Supplementary concepts

  • Acromesomelic dysplasia
  • Cranioectodermal Dysplasia