{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:23:47Z","timestamp":1789532627879,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital de Especialidades Eugenio Espejo"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Dyggve\u2013Melchior\u2013Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia characterized by dwarfism, coarse facial features, and intellectual disability. Caused by loss-of-function variants in the DYM gene, which encodes dymeclin, DMC is predominantly reported in consanguineous populations but remains poorly studied in South America. Methods: We report a 21-year-old Ecuadorian male with clinical features suggestive of DMC. Comprehensive clinical, radiological, and genetic evaluations were conducted, including clinical exome sequencing and Sanger sequencing, followed by an in silico analysis to assess the structural and functional consequences of the identified variant. Results: Exome sequencing identified a homozygous c.1878delA (p.Lys626fs) frameshift variant in the DYM gene, which was confirmed by Sanger sequencing as inherited from heterozygous parents. Variants of uncertain significance were detected in other skeletal dysplasia-related genes but did not correlate with the phenotype. A comprehensive review of reported DYM variants was also conducted. Conclusions: This report documents the first case of DMC in Ecuador and the second in South America, expanding the global understanding of DMC\u2019s genetic diversity. It underscores the value of next-generation sequencing in rare disease diagnostics and highlights the critical need for inclusive genomic research in underrepresented populations to improve the understanding of genetic heterogeneity and rare disease epidemiology.<\/jats:p>","DOI":"10.3390\/genes16050490","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dyggve\u2013Melchior\u2013Clausen Syndrome in Ecuador: Expanding Knowledge on a Rare Genetic Disorder"],"prefix":"10.3390","volume":"16","author":[{"given":"Carlos","family":"Reyes-Silva","sequence":"first","affiliation":[{"name":"Unidad de Gen\u00e9tica, Hospital de Especialidades Eugenio Espejo, Quito 170403, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseline","family":"Gallardo-Vizuete","sequence":"additional","affiliation":[{"name":"Posgrado de Endocrinolog\u00eda, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Guzm\u00e1n-Ac\u00e1n","sequence":"additional","affiliation":[{"name":"Posgrado de Endocrinolog\u00eda, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-1763","authenticated-orcid":false,"given":"Gabriela","family":"Jaramillo-Koupermann","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular, Subproceso de Anatom\u00eda Patol\u00f3gica, Hospital de Especialidades Eugenio Espejo, Quito 170403, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-6618","authenticated-orcid":false,"given":"Alejandro","family":"Cabrera-Andrade","sequence":"additional","affiliation":[{"name":"Grupo de Bio-Quimioinform\u00e1tica, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"},{"name":"Escuela de Enfermer\u00eda, Facultad de Ciencias de la Salud, Universidad de Las Am\u00e9ricas, Quito 170125, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41431-019-0508-0","article-title":"Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database","volume":"28","author":"Lambert","year":"2020","journal-title":"Eur. 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