000162635 001__ 162635
000162635 005__ 20251017144621.0
000162635 0247_ $$2doi$$a10.3390/ijms26167964
000162635 0248_ $$2sideral$$a145174
000162635 037__ $$aART-2025-145174
000162635 041__ $$aeng
000162635 100__ $$adel Rincón, Julia
000162635 245__ $$aAI-Based Facial Phenotyping Supports a Shared Molecular Axis in PACS1-, PACS2-, and WDR37-Related Syndromes
000162635 260__ $$c2025
000162635 5060_ $$aAccess copy available to the general public$$fUnrestricted
000162635 5203_ $$aDespite significant advances in gene discovery, the molecular basis of many rare genetic disorders remains poorly understood. The concept of disease modules, clusters of functionally related genes whose disruption leads to overlapping phenotypes, offers a valuable framework for interpreting these conditions. However, identifying such relationships remains particularly challenging in ultra-rare syndromes due to the limited number of documented cases. We hypothesized that AI-based facial phenotyping could aid in identifying shared molecular mechanisms by detecting phenotypic convergence among clinically related syndromes. To test this, we used Schuurs–Hoeijmakers syndrome (SHMS; OMIM #615009), caused by a recurrent de novo variant in PACS1, as a model to explore potential phenotypic and functional associations with PACS2-related disorder (DEE66; OMIM #618067) and WDR37-related disorder (NOCGUS; OMIM #618652). Facial photographs of individuals with SHMS were analyzed using the DeepGestalt and GestaltMatcher algorithms. In addition to consistently recognizing SHMS as a distinct clinical entity, the algorithms frequently matched DEE66 and NOCGUS, suggesting a shared facial gestalt. Binary comparisons further confirmed overlapping craniofacial features among the three disorders. These findings were supported by literature review, indicating clinical overlapping and potential functional associations. Overall, our results confirm the presence of consistent facial similarities among PACS1-, PACS2-, and WDR37-related syndromes and highlight the utility of AI-driven facial phenotyping as a complementary tool for uncovering clinically relevant relationships in ultra-rare genetic disorders.
000162635 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/B32-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI23-01370$$9info:eu-repo/grantAgreement/ES/UZ/JIUZ-2023-SAL-06
000162635 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000162635 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000162635 700__ $$0(orcid)0000-0001-6858-1575$$aGil-Salvador, Marta$$uUniversidad de Zaragoza
000162635 700__ $$aLucia-Campos, Cristina$$uUniversidad de Zaragoza
000162635 700__ $$aAcero, Laura$$uUniversidad de Zaragoza
000162635 700__ $$aTrujillano, Laura
000162635 700__ $$0(orcid)0000-0001-9962-2157$$aArnedo, María$$uUniversidad de Zaragoza
000162635 700__ $$aPamplona, Pilar$$uUniversidad de Zaragoza
000162635 700__ $$0(orcid)0000-0002-0023-8137$$aAyerza-Casas, Ariadna$$uUniversidad de Zaragoza
000162635 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, Beatriz$$uUniversidad de Zaragoza
000162635 700__ $$0(orcid)0000-0002-5732-2209$$aRamos, Feliciano J.$$uUniversidad de Zaragoza
000162635 700__ $$0(orcid)0000-0003-3203-6254$$aPié, Juan$$uUniversidad de Zaragoza
000162635 700__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, Ana$$uUniversidad de Zaragoza
000162635 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000162635 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000162635 7102_ $$11011$$2670$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Pediatría
000162635 773__ $$g26, 16 (2025), 7964 [13 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000162635 8564_ $$s2189728$$uhttps://zaguan.unizar.es/record/162635/files/texto_completo.pdf$$yVersión publicada
000162635 8564_ $$s2582626$$uhttps://zaguan.unizar.es/record/162635/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
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000162635 951__ $$a2025-10-17-14:21:59
000162635 980__ $$aARTICLE