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 journalArticle


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.

Original languageEnglish
JournalClinical Genetics
Publication statusAccepted/In press - Jan 1 2018



  • DYNC2LI1
  • Ellis-van Creveld syndrome
  • Genotype-phenotype correlations
  • Jeune syndrome
  • Short-rib thoracic dysplasia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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