{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:00:01Z","timestamp":1778868001988,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.110909\/2025\u201000; 88887.113708\/2025\u201000"],"award-info":[{"award-number":["88887.110909\/2025\u201000; 88887.113708\/2025\u201000"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/08028\u20101; 2022\/03980\u20105; 2023\/07389\u20102; 2023\/16666\u20100; 2023\/16839\u20101; 2023\/09879\u20107"],"award-info":[{"award-number":["2013\/08028\u20101; 2022\/03980\u20105; 2023\/07389\u20102; 2023\/16666\u20100; 2023\/16839\u20101; 2023\/09879\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Xia\u2013Gibbs syndrome (XGS) is a rare intellectual disability (ID) syndrome caused by\n                    <jats:italic>de novo AHDC1<\/jats:italic>\n                    pathogenic variants. We characterized clinical and molecular features of 16 Brazilian patients with XGS. Patient data were collected through semistructured interviews with family members, reanalysis of previous health and genetic assessments, and clinical reports from physicians. Genomic variants and their segregation were validated via Sanger sequencing. Statistical analyses were conducted to evaluate genotype\u2013phenotype associations. Twelve novel\n                    <jats:italic>AHDC1<\/jats:italic>\n                    causative variants were documented. ID, hypotonia, motor developmental delay, and varied nonspecific facial dysmorphisms were observed in all patients, while speech impairment and autism spectrum disorder were present in nearly all. Three frequent phenotypes, not previously reported, were identified: hyperphagia\/food obsession, genital\/gonadal alterations in males, and shortening of the Achilles tendon. Additionally, our findings provide statistically significant support for previously reported genotype\u2013phenotype associations between pathogenic variants in the first half of the\n                    <jats:italic>AHDC1<\/jats:italic>\n                    coding region and the occurrence of epilepsy and scoliosis. We also propose a novel association between N\u2010terminal variants and developmental regression. In summary, our results broaden the clinical phenotype of XGS, with musculoskeletal and genital\/gonadal abnormalities highlighting the multisystem involvement in this condition, beyond neurodevelopmental deficits. Comprehensive phenotypic assessments in all identified XGS cases are recommended to accurately recognize and associate novel clinical signs with XGS.\n                  <\/jats:p>","DOI":"10.1111\/cge.14777","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T02:44:01Z","timestamp":1749696241000},"page":"654-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical and Molecular Characterization of Xia\u2013Gibbs Syndrome: Expanding the Phenotypic Spectrum in a Brazilian Cohort"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6136-1925","authenticated-orcid":false,"given":"Ma\u00edsa Ganz Sanchez","family":"Sennes","sequence":"first","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-2236","authenticated-orcid":false,"given":"Laura Machado Lara","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-8799","authenticated-orcid":false,"given":"Matheus Augusto Ara\u00fajo","family":"Castro","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovana Manilli","family":"Toccoli","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics Federal University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-1692","authenticated-orcid":false,"given":"Sofia de Oliveira","family":"Farias","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0483-8797","authenticated-orcid":false,"given":"Davi Mendes Campo","family":"Fialho","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-4673","authenticated-orcid":false,"given":"Eny Maria Goloni","family":"Bertollo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Sao Jos\u00e9 do Rio Preto  S\u00e3o Jos\u00e9 do Rio Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0959-0695","authenticated-orcid":false,"given":"Erika Cristina","family":"Pavarino","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Sao Jos\u00e9 do Rio Preto  S\u00e3o Jos\u00e9 do Rio Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larissa Sampaio","family":"de Athayde","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo, Faculdade de Medicina, Departamento de Neurologia Mendelics Genomic Analysis  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia Barbosa","family":"Buck","sequence":"additional","affiliation":[{"name":"Anhembi Morumbi University  Piracicaba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Bet\u00e2nia Pereira","family":"Toralles","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Federal University of Bahia  Salvador Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4344-9698","authenticated-orcid":false,"given":"Maria Isabel","family":"Melaragno","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics Federal University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6397-1301","authenticated-orcid":false,"given":"Mariluce","family":"Riegel\u2010Giugliani","sequence":"additional","affiliation":[{"name":"Casa dos Raros, Center for Comprehensive Care and Training in Rare Diseases Anthony Daher Laboratory, Casa dos Raros  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Marquezani","family":"Spolador","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Pain and Palliative Care Instituto da Crian\u00e7a, Clinics Hospital of University of Sao Paulo Faculty of Medicine  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-6608","authenticated-orcid":false,"given":"Paulo Alberto","family":"Otto","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline Brand\u00e3o","family":"Piai","sequence":"additional","affiliation":[{"name":"Genetics Unit Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7577-9122","authenticated-orcid":false,"given":"Fernando","family":"Kok","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo, Faculdade de Medicina, Departamento de Neurologia Mendelics Genomic Analysis  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceres Schmitz","family":"Cechella","sequence":"additional","affiliation":[{"name":"Cechella Medical Clinic  Novo Hamburgo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3253-4448","authenticated-orcid":false,"given":"Carla","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Clinton","family":"Llerena","sequence":"additional","affiliation":[{"name":"National Institute Fernandes Figueira \u2010 Fiocruz  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-6777","authenticated-orcid":false,"given":"D\u00e9bora Romeo","family":"Bertola","sequence":"additional","affiliation":[{"name":"Genetics Unit Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salmo","family":"Raskin","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Child and Adolescent, Department of Pediatrics Federal University of Paran\u00e1  Curitiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-1300","authenticated-orcid":false,"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Genetics Unit Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-8605","authenticated-orcid":false,"given":"Ana Cristina Victorino","family":"Krepischi","sequence":"additional","affiliation":[{"name":"Institute of Biosciences, Department of Genetics and Evolutionary Biology Human Genome and Stem Cell Research Center, University of Sao Paulo  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"issue":"12","key":"e_1_2_12_2_1","article-title":"Xia\u2010Gibbs Syndrome: A Review of 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