Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum.

Autor: Atique Tacla M; Department of Translational Medicine, Area of Medical Genetics and Genomic Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil., de Mello Copelli M; Department of Translational Medicine, Area of Medical Genetics and Genomic Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil., Pairet E; Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium., Monlleó IL; Clinical Genetics Service, University Hospital, Medical Genetics Sector, Faculty of Medicine, Federal University of Alagoas - UFAL, Maceió, AL, Brazil., Ribeiro EM; Medical Genetics Service, Hospital Infantil Albert Sabin - HIAS, Fortaleza, CE, Brazil., Lustosa Mendes E; Assistance Center for Cleft Lip and Palate - CAIF-HT, Curitiba, PR, Brazil., Helaers R; Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium., Vieira TP; Department of Translational Medicine, Area of Medical Genetics and Genomic Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil., Vikkula M; Human Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium., Gil-da-Silva-Lopes VL; Department of Translational Medicine, Area of Medical Genetics and Genomic Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil. vgslopes@unicamp.br.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2023 Nov 06. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.1038/s41431-023-01488-5
Abstrakt: This study describes genomic findings among individuals with both orofacial clefts (OC) and microphthalmia/anophthalmia/coloboma (MAC) recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole Exome Sequencing (WES) were performed in 17 individuals with OC-MAC. Clinical interpretation of molecular findings was based on data available at the BDCA and on re-examination. No copy number variants (CNVs) classified as likely pathogenic or pathogenic were detected by CMA. WES allowed a conclusive diagnosis in six individuals (35.29%), two of them with variants in the CHD7 gene, and the others with variants in the TFAP2A, POMT1, PTPN11, and TP63 genes with the following syndromes: CHARGE, CHD7-spectrum, Branchiooculofacial, POMT1-spectrum, LEOPARD, and ADULT. Variants of uncertain significance (VUS) possibly associated to the phenotypes were found in six other individuals. Among the individuals with VUSes, three individuals presented variants in genes associated to defects of cilia structure and/or function, including DYNC2H1, KIAA0586, WDR34, INTU, RPGRIP1L, KIF7, and LMNA. These results show that WES was the most effective molecular approach for OC-MAC in this cohort. This study also reinforces the genetic heterogeneity of OC-MAC, and the importance of genes related to ciliopathies in this phenotype.
(© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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