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Lara Carvalho, Laura Machado ; D'Angelo, Carla Sustek ; Villela, Darine ; da Costa, Silvia Souza ; de Lima Jorge, Alexander Augusto ; da Silva, Israel Tojal ; Scliar, Marilia de Oliveira ; Chaves, Luiza Dias ; Victorino Krepischi, Ana Cristina ; Koiffmann, Celia Priszkulnik ; Rosenberg, Carla

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Obesity; v. N/A, p. 5-pg., 2022-05-21.

Resumo

Background: Syndromic obesity (SO) refers to obesity with additional phenotypes, including intellectual disability (ID)/developmental delay (DD), dysmorphic features, or organ-specific abnormalities. SO is rare, has high phenotypic variability, and frequently follows a monogenic pattern of inheritance. However, the genetic etiology of most cases of SO has not been elucidated. Subjects and methods: In this study, we investigated 20 SO patients by whole-exome sequencing (WES) trios to identify causal genetic variants. Results: 4/20 patients had negative results for array comparative genomic hybridization (aCGH) analyses. In the remaining 15 patients, in addition to SNVs and indels, CNVs were also evaluated. Pathogenic/likely pathogenic (P/LP) SNVs/indels were detected in 6/20 patients (involving MED13L, AHDC1, EHMT1, MYT1L, GR1A3, and SETD1A), while two patients carried an inherited VUS. In addition, P/LP CNVs were observed in 3/15 patients (involving SATG2, KlAA0442, and ME1S2). Conclusions: All nine detected P/LP variants involved genes already known to lead to syndromic ID/DD; however, for only two genes (EHMT1 and MYT1L) is the link with obesity well established. This is the first study applying a comprehensive genomic investigation of an SO cohort, showing a high diagnostic yield (-47%). Additionally, our findings suggested that several known ID/DD genes may also predispose individuals to SO. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 18/08486-3 - Investigação das bases genéticas da obesidade sindrômica e de mecanismos moleculares relacionados à sua fisiopatologia
• Beneficiário: Laura Machado Lara Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/50981-5 - Uso de arrays genomicos de alta resolucao e next generation sequencing no diagnostico de deficiencia mental e anomalias congenitas
• Beneficiário: Francine Campagnari Guilhem
• Modalidade de apoio: Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE