{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:06Z","timestamp":1760148186631,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,9]],"date-time":"2023-04-09T00:00:00Z","timestamp":1680998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad Nacional Autonoma de Mexico","award":["UNAM-PAPIIT IN230520"],"award-info":[{"award-number":["UNAM-PAPIIT IN230520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Ellis\u2013van Creveld syndrome (EvCS) is an autosomal recessive ciliopathy with a disproportionate short stature, polydactyly, dystrophic nails, oral defects, and cardiac anomalies. It is caused by pathogenic variants in the EVC or EVC2 genes. To obtain further insight into the genetics of EvCS, we identified the genetic defect for the EVC2 gene in two Mexican patients. Methods: Two Mexican families were enrolled in this study. Exome sequencing was applied in the probands to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in the parents. Finally, a prediction of the three-dimensional structure of the mutant proteins was made. Results: One patient has a compound heterozygous EVC2 mutation: a novel heterozygous variant c.519_519 + 1delinsT inherited from her mother, and a heterozygous variant c.2161delC (p.L721fs) inherited from her father. The second patient has a previously reported compound heterozygous EVC2 mutation: nonsense mutation c.645G &gt; A (p.W215*) in exon 5 inherited from her mother, and c.273dup (p.K92fs) in exon 2 inherited from her father. In both cases, the diagnostic was Ellis\u2013van Creveld syndrome. Three-dimensional modeling of the EVC2 protein showed that truncated proteins are produced in both patients due to the generation of premature stop codons. Conclusion: The identified novel heterozygous EVC2 variants, c.2161delC and c.519_519 + 1delinsT, were responsible for the Ellis\u2013van Creveld syndrome in one of the Mexican patients. In the second Mexican patient, we identified a compound heterozygous variant, c.645G &gt; A and c.273dup, responsible for EvCS. The findings in this study extend the EVC2 mutation spectrum and may provide new insights into the EVC2 causation and diagnosis with implications for genetic counseling and clinical management.<\/jats:p>","DOI":"10.3390\/genes14040887","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Compound Heterozygous EVC2 Gene Variants in Two Mexican Families with Ellis\u2013van Creveld Syndrome"],"prefix":"10.3390","volume":"14","author":[{"given":"Nancy","family":"Negrete-Torres","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Oncolog\u00eda Molecular, Laboratorio 5, Edificio A4, Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"},{"name":"Laboratorio de Gen\u00e9tica, Escuela Nacional de Ciencias Biol\u00f3gicas Zacatenco, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda del Carmen","family":"Chima-Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Centro M\u00e9dico Nacional \u201c20 de Noviembre\u201d, ISSSTE, Ciudad de M\u00e9xico 03229, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernesto Antonio","family":"Sierra-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Centro M\u00e9dico Nacional \u201c20 de Noviembre\u201d, ISSSTE, Ciudad de M\u00e9xico 03229, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"S\u00e1nchez-Ramos","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Oncolog\u00eda Molecular, Laboratorio 5, Edificio A4, Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4011-9121","authenticated-orcid":false,"given":"Isela","family":"\u00c1lvarez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica, Escuela Nacional de Ciencias Biol\u00f3gicas Zacatenco, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 07738, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Reyes-Reali","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda, Unidad de Morfofisiolog\u00eda y Funci\u00f3n, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Isabel","family":"Mendoza-Ramos","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda, Unidad de Morfofisiolog\u00eda y Funci\u00f3n, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efra\u00edn","family":"Garrido-Guerrero","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular, CINVESTAV-IPN, Ciudad de M\u00e9xico 07360, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dante","family":"Amato","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Oncolog\u00eda Molecular, Laboratorio 5, Edificio A4, Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-1085","authenticated-orcid":false,"given":"Claudia Fabiola","family":"M\u00e9ndez-Catal\u00e1","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Oncolog\u00eda Molecular, Laboratorio 5, Edificio A4, Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"},{"name":"Divisi\u00f3n de Investigaci\u00f3n y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-4081","authenticated-orcid":false,"given":"Glustein","family":"Pozo-Molina","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Oncolog\u00eda Molecular, Laboratorio 5, Edificio A4, Carrera de M\u00e9dico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo Ren\u00e9","family":"M\u00e9ndez-Cruz","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda, Unidad de Morfofisiolog\u00eda y Funci\u00f3n, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Tlalnepantla 54090, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/gm275","article-title":"A systems-biology approach to understanding the ciliopathy disorders","volume":"3","author":"Lee","year":"2011","journal-title":"Genome Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4843","article-title":"Motile and non-motile cilia 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