Significance of GNAS mutations for morbid obesity in children.

Ramil R Salakhov; Rita I Khusainova; Olga V Vasyukova; Daria A Kopytina; Bulat I Yalaev; Yulia S Karpova; Pavel L Okorokov; Valentina A Peterkova; Ildar R Minniakhmetov; Natalia G Mokrysheva

doi:10.1186/s40246-025-00781-2

PubMed · 41029821

Significance of GNAS mutations for morbid obesity in children.

Ramil R Salakhov·Rita I Khusainova·Olga V Vasyukova·Daria A Kopytina·Bulat I Yalaev·Yulia S Karpova·Pavel L Okorokov·Valentina A Peterkova·Ildar R Minniakhmetov·Natalia G Mokrysheva

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Abstract

BACKGROUND: Hereditary forms of obesity are characterized by early severe heterogeneous manifestations of the phenotype along with a rapid progression to morbid obesity, primary due to pathogenic variants of certain genes. Most forms are characterized by moderate to severe neuropsychic developmental delays, dysmorphic features and organ-specific developmental anomalies. RESULT: We searched for hereditary causes of morbid obesity in children by exome sequencing. As a result, we have identified 5 variants in the GNAS locus, two of which were identified for the first time: NM_000516.7(GNAS):c.201del, (p.Phe68Leufs*32) and NM_000516.7(GNAS):c.586 - 18_591del. Children showed tolerance to parathyroid hormone and thyroid-stimulating hormone. It has been observed that almost all the children with frameshift variants or nonsense mutations presented with subcutaneous ossifications. CONCLUSIONS: The search for variants in a group of patients with morbid obesity, as conducted in our research, reaffirms the need for use molecular genetic testing to determine the main diagnosis and facilitate early detection of the disease. This is particularly relevant given the wide clinical variability of monogenic forms of obesity.

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Humans Chromogranins GTP-Binding Protein alpha Subunits, Gs Child Obesity, Morbid Male Female Mutation Child, Preschool Adolescent Genetic Predisposition to Disease Exome Sequencing Phenotype GNAS Albright's hereditary osteodystrophy Morbid obesity Pseudohypoparathyroidism (PHP)Journal Article

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Ramil R Salakhov, Rita I Khusainova, Olga V Vasyukova, Daria A Kopytina, Bulat I Yalaev, Yulia S Karpova, Pavel L Okorokov, Valentina A Peterkova, Ildar R Minniakhmetov, Natalia G Mokrysheva. 2025-09-30. Significance of GNAS mutations for morbid obesity in children.. https://doi.org/10.1186/s40246-025-00781-2

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