{"id":11127,"date":"2026-03-04T00:00:00","date_gmt":"2026-03-04T00:00:00","guid":{"rendered":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1753212"},"modified":"2026-03-04T00:00:00","modified_gmt":"2026-03-04T00:00:00","slug":"co-occurring-dmd-gja1-and-novel-fyco1-variants-in-a-proband-from-a-consanguineous-oculodentodigital-dysplasia-family-a-rare-multi-locus-case-report","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2026\/03\/04\/co-occurring-dmd-gja1-and-novel-fyco1-variants-in-a-proband-from-a-consanguineous-oculodentodigital-dysplasia-family-a-rare-multi-locus-case-report\/","title":{"rendered":"Co-occurring DMD, GJA1, and novel FYCO1 variants in a proband from a consanguineous oculodentodigital dysplasia family: a rare multi-locus case report"},"content":{"rendered":"Whole-exome sequencing of the proband and the family revealed multi-locus pathogenic variants (MGVs) leading to multiple genetic diagnoses (MGDs), explaining the complex phenotype with neuromuscular, ocular, and craniofacial abnormalities. The proband harbored a de novo hemizygous DMD frameshift variant consistent with Duchenne muscular dystrophy, a paternally inherited heterozygous GJA1 in-frame indel associated with oculodentodigital dysplasia (ODDD), and a novel homozygous FYCO1 nonsense variant causing congenital cataract. Fraction of ROH (FROH) analyses indicated extended autozygosity, which is indicative of second-cousin-level consanguinity. The novel FYCO1 variant was located within one of the indicative ROHs, supporting identity by descent. Structural analysis predicted truncating or domain-disrupting effects across all three genes, aligning with the multisystem phenotype. The coexistence of the DMD, GJA1, and novel FYCO1 variants in a single individual is exceptionally rare. To our knowledge, this represents the first report of such a multi-locus combination, highlighting the diagnostic complexity of combined recessive, dominant, and de novo events in a proband born in a consanguineous ODDD family.","protected":false},"excerpt":{"rendered":"<p>Whole-exome sequencing of the proband and the family revealed multi-locus pathogenic variants (MGVs) leading to multiple genetic diagnoses (MGDs), explaining the complex phenotype with neuromuscular, ocular, and craniofacial abnormalities. The proband &#8230;<\/p>\n","protected":false},"author":459,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,80,12,13],"tags":[71],"class_list":["post-11127","post","type-post","status-publish","format-standard","hentry","category-articulos","category-case-report","category-enfermedades-raras","category-frontiers-in-genetics","tag-frontgenet"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11127","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/users\/459"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=11127"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11127\/revisions"}],"predecessor-version":[{"id":11128,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/11127\/revisions\/11128"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=11127"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=11127"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=11127"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}