Whole Exome Sequencing Revealed Paternal Inheritance of Obesity-related Genetic Variants in a Family with an Exclusively Breastfed Infant
Hazal Banu Olgun Çelebioğlu1, Ayşe Pınar Öztürk3, Şükran Poyrazoğlu3, Feyza Nur Tuncer11Istanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkiye2Istanbul University, Institute of Graduate Studies in Health Sciences, Istanbul, Turkiye
3Istanbul University, Istanbul Faculty of Medicine, Department of Pediatrics, Pediatric Endocrinology Unit, Istanbul, Turkiye
INTRODUCTION: Obesity is a serious health problem that progressively affects individuals’ lives with comorbidities, such as heart disease, stroke, and diabetes mellitus. Since its prevalence has increased, particularly in children less than five years old, its genetic and environmental causes should be determined for prevention and control of the disease. The aim of this study was to detect underlying genetic risk factors in a family with an exclusively breastfed obese infant.
METHODS: A three-generation family was recruited to be evaluated for obesity. Detailed examinations along with body mass index (BMI) calculations were performed on available family members. Whole exome sequencing (WES) was performed on a 7-month-old obese infant. Bioinformatic analyses were performed on the Genomize SEQ platform with variant filtering at minor allele frequencies <1% for all normal populations. Sanger sequencing was applied in variant confirmation and family segregation.
RESULTS: Neuro-motor developmental features were normal and genetic syndromes were excluded from the index. Early-onset severe obesity (+4.25 standard deviation score weight-for-height) was evident in index case; his father and grandmother were also obese (BMIs 38.1 kg/m2 and 31.3 kg/m2, respectively). WES analysis revealed deleterious variants in SH2B1, PDE11A, ADCY3, and CAPN10 genes previously associated with obesity. All variants were evaluated as novel candidates for obesity, except PDE11A, and family segregation confirmed paternal inheritance.
DISCUSSION AND CONCLUSION: This study confirmed the paternal inheritance of all potentially deleterious obesity-related variants. The cumulative effect of individual variants might explain the obesity phenotype in this family. The infant is recommended to be followed up periodically due to increased risk for later childhood obesity.
Manuscript Language: English
