{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T21:42:18Z","timestamp":1794433338774,"version":"4.9.1"},"reference-count":30,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,7,9]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib\u2013polydactyly 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\n                      <jats:italic>EVC<\/jats:italic>\n                      and\n                      <jats:italic>EVC2<\/jats:italic>\n                      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,\n                      <jats:italic>WDR35<\/jats:italic>\n                      ,\n                      <jats:italic>GLI1<\/jats:italic>\n                      ,\n                      <jats:italic>DYNC2LI1<\/jats:italic>\n                      ,\n                      <jats:italic>PRKACA<\/jats:italic>\n                      ,\n                      <jats:italic>PRKACB<\/jats:italic>\n                      and\n                      <jats:italic>SMO<\/jats:italic>\n                      . They all code for proteins located in the primary cilia, playing a key role in signal transduction of the Hedgehog pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our detection rate in the cohort of 45 families was of 91.11%, with variants identified in\n                      <jats:italic>EVC\/EVC2<\/jats:italic>\n                      (77.8%),\n                      <jats:italic>DYNC2H1<\/jats:italic>\n                      (6.7%),\n                      <jats:italic>DYNC2LI1<\/jats:italic>\n                      (2.2%),\n                      <jats:italic>SMO<\/jats:italic>\n                      (2.2%) or\n                      <jats:italic>PRKACB<\/jats:italic>\n                      (2.2%). No distinctive feature was remarkable of a specific genotype\u2013phenotype correlation. Interestingly, we identified a high proportion of heterozygous deletions in\n                      <jats:italic>EVC\/EVC2<\/jats:italic>\n                      of variable sizes (26.92%), mostly inherited from the mother, and probably resulting from recombinations involving Alu sequences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We confirmed that\n                      <jats:italic>EVC<\/jats:italic>\n                      and\n                      <jats:italic>EVC2<\/jats:italic>\n                      are the major genes involved in the EVC phenotype and highlighted the high prevalence of previously unreported CNVs (Copy Number Variation).\n                    <\/jats:p>\n                  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