Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome

M. Niceta, K. Margiotti, M.C. Digilio, V. Guida, A. Bruselles, S. Pizzi, A. Ferraris, L. Memo, N. Laforgia, M.L. Dentici, F. Consoli, I. Torrente, V.L. Ruiz-Perez, B. Dallapiccola, B. Marino, A. De Luca, M. Tartaglia

Research output: Contribution to journalArticlepeer-review


Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with 3 affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYNC2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the 3 affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a truncating change (p.Val141*) in 2 siblings with EvC from a second family, while a newborn with a more severe phenotype carried 2 DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Original languageEnglish
Pages (from-to)632-639
Number of pages8
JournalClinical Genetics
Issue number3
Publication statusPublished - 2018


  • DYNC2LI1
  • Ellis-van Creveld syndrome
  • genotype-phenotype correlations
  • Jeune syndrome
  • short-rib thoracic dysplasia
  • messenger RNA
  • adolescent
  • adult
  • aortic coarctation
  • Article
  • brachydactyly
  • case report
  • child
  • clinical article
  • clinical feature
  • DYNC2LI1 gene
  • Ellis van Creveld syndrome
  • female
  • gene
  • gene mutation
  • genotype phenotype correlation
  • heterozygosity
  • human
  • hypodontia
  • infant
  • nail dysplasia
  • newborn
  • patent ductus arteriosus
  • phenotype
  • polydactyly
  • preschool child
  • priority journal
  • Sanger sequencing
  • sibling
  • supernumerary tooth
  • thorax malformation
  • vertebral canal stenosis
  • whole exome sequencing
  • young adult


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