Genetic investigation of syndromic forms of obesity

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,...

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Bibliographic Details
Published in:International Journal of Obesity 2022-09, Vol.46 (9), p.1582-1586
Main Authors: Carvalho, Laura Machado Lara, D'Angelo, Carla Sustek, Villela, Darine, da Costa, Silvia Souza, de Lima Jorge, Alexander Augusto, da Silva, Israel Tojal, de Oliveira Scliar, Marília, Chaves, Luiza Dias, Krepischi, Ana Cristina Victorino, Koiffmann, Celia Priszkulnik, Rosenberg, Carla
Format: Article
Language:English
Subjects:
Abnormalities
Etiology
Genes
Genetic diversity
Genetic variability
Genetic variance
Genomics
Heredity
Hybridization
Intellectual disabilities
Obesity
Phenotypes
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Summary: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. In this study, we investigated 20 SO patients by whole-exome sequencing (WES) trios to identify causal genetic variants. 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, GRIA3, and SETD1A), while two patients carried an inherited VUS. In addition, P/LP CNVs were observed in 3/15 patients (involving SATG2, KIAA0442, and MEIS2). 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.
ISSN:0307-0565
1476-5497
DOI:10.1038/s41366-022-01149-5