ESPE Abstracts

Objective: This study investigated the genetic etiology and clinical phenotype of non-syndromic childhood and adolescent obesity.

Methods: A total of 392 non-syndromic obese children aged 7-14 years old who were hospitalized in Department of Endocrinology. Whole exon sequencing was used to screen the potential genetic causes and analyze CNV and 79 reported obesity candidate genes.

Results: 1) A total of 392 non-syndromic children and adolescents with obesity were included in this study, all of which developed obesity symptoms under 10 years old, including 302 boys and 90 girls, with a male-to-female ratio of 3.38:1. The average age of seeking medical treatment was 10.37±1.74 years old. The mean BMI was 26.92±3.41 kg/m2, the mean height Z-value was 1.05±1.19, the mean weight Z-value was 3.19±0.95, and the mean BMI-Z value was 2.98±0.71. 2) In this study, 32 patients (32/392,8.2%) were screened with 18 non-syndromic obesity genes. Including UCP3, MC4R, PCSK1, NR0B2, NRP1, SEMA3B, DYRK1B, MRAP2, NRP2, NTRK2, PLXNA3, PLXNA4, PPARG, SEMA3C, SEMA3F, SEMA3G, SIM1.UCP3 gene (6/32) and MC4R gene (4/32) were the most common. ACMG rating was LP in 7 cases, and ACMG rating was VUS in 24 cases with a Bayes score greater than 2. No patients with copy number variation were found in this study. 3) Correlation analysis between clinical phenotype and genetics: There were 7 patients was rating LP by ACMG guideline, 1 was male and 6 was female; The onset age of obesity was less than 10 years old, the mean age of diagnosis was 9.89±1.96 years old, the mean weight was 54.2±12.64 kg, the mean height was 142.32±12.85cm, the mean BMI was 26.34±2.18, and the mean weight Z-value was 1.74±1.72. The mean height Z-value was 0.74±0.87, and the mean BMI-Z value was 2.84±0.48. There were 5 cases with elevated uric acid, 5 cases with family history, 4 cases with fatty liver, 2 cases with impaired glucose tolerance, 5 cases with insulin resistance, 3 cases with hypertriglyceridemia, 2 cases with metabolic syndrome, and 5 cases with precocious puberty.

Conclusion: This study found that 8.2% of children and adolescents with non-syndromic obesity in China carry single gene variants of autosomal dominant obesity, single gene variants are more common in females, and UCP3 and MC4R gene variants are the most common, which may be the hot genes of non-syndromic obesity in China.