RT Journal Article
SR Electronic
T1 Ellis-Van Creveld Syndrome: Clinical and Molecular Analysis of 50 Individuals
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP jmedgenet-2022-108435
DO 10.1136/jmg-2022-108435
A1 Marion Aubert-Mucca
A1 Céline Huber
A1 Genevieve Baujat
A1 Caroline Michot
A1 Mohammed Zarhrate
A1 Marc Bras
A1 Lucile Boutaud
A1 Valérie Malan
A1 Tania Attie-Bitach
A1 Clinical Contributors
A1 Valerie Cormier-Daire
YR 2022
UL http://jmg.bmj.com/content/early/2022/08/04/jmg-2022-108435.abstract
AB Background Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib–polydactyly subgroup. Major signs are ectodermal dysplasia, chondrodysplasia, polydactyly and congenital cardiopathy, with a high degree of variability in phenotypes ranging from lethal to mild clinical presentations. The EVC and EVC2 genes are the major genes causative of EVC syndrome. However, an increased number of genes involved in the ciliopathy complex have been identified in EVC syndrome, leading to a better understanding of its physiopathology, namely, WDR35, GLI1, DYNC2LI1, PRKACA, PRKACB and SMO. They all code for proteins located in the primary cilia, playing a key role in signal transduction of the Hedgehog pathways.Methods The aim of this study was the analysis of 50 clinically identified EVC cases from 45 families to further define the phenotype and molecular bases of EVC.Results Our detection rate in the cohort of 45 families was of 91.11%, with variants identified in EVC/EVC2 (77.8%), DYNC2H1 (6.7%), DYNC2LI1 (2.2%), SMO (2.2%) or PRKACB (2.2%). No distinctive feature was remarkable of a specific genotype–phenotype correlation. Interestingly, we identified a high proportion of heterozygous deletions in EVC/EVC2 of variable sizes (26.92%), mostly inherited from the mother, and probably resulting from recombinations involving Alu sequences.Conclusion We confirmed that EVC and EVC2 are the major genes involved in the EVC phenotype and highlighted the high prevalence of previously unreported CNVs (Copy Number Variation).Data supporting figures 1–4, tables 1–2 and online supplemental tables 1–2 are not publicly available in order to protect patient privacy.