ABSTRACT
OBJECTIVE@#To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity.@*METHODS@#A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic.@*CONCLUSION@#The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Subject(s)
Female , Humans , Child, Preschool , Computational Biology , East Asian People , Genetic Counseling , Genomics , Mutation , Obesity, Morbid/genetics , Pediatric Obesity/geneticsABSTRACT
La obesidad constituye un problema grave de salud pública. La OMS la define como una acumulaciónanormal o excesiva de grasa que puede ser perjudicial para la salud. La prevalencia se ha incrementado.Enfermedad crónica, compleja y multifactorial, en la que interaccionan factores genéticos y ambientales. Elíndice de Quételet o índice de masa corporal (IMC), es usado para estimar la gravedad. La valoración inicialdebe incluir exploración física y valorar el desarrollo puberal. Se asocia, con complicaciones inmediatas,int e rmedi a s y t a rdí a s . El t r a t ami ento e s multidisciplinario e individualizado. La cirugía en la población pediátrica está limitada. No se debe perder de vista que la solución ideal a este problema es laprevención.
Obesity is a serious public health problema. WHO defines it as an accumulation of abnormal or excessive fat that can be harmful to health. The prevalence has increased. It's a chronic, complex and multifactorial patology, in which genetic and environmental factors interact. Quetelet index or body mass index is used to estímate the severity. The initial assessment should include physical examination and assess pubertal development. It is associated with immediate, intermédiate and late complications. The treatment is multidisciplinary and individualized. Surgery in the pediatric population is limited. Do not forget that the ideal solution to this problema is prevention.
Subject(s)
Humans , Male , Adolescent , Adult , Female , Child , Young Adult , Obesity, Morbid/classification , Obesity, Morbid/complications , Obesity, Morbid/diagnosis , Obesity, Morbid/diet therapy , Obesity, Morbid/etiology , Obesity, Morbid/genetics , Obesity, Morbid/history , Obesity, Morbid/pathology , Obesity, Morbid/therapy , Body Mass Index , Obesity, Morbid/physiopathology , Obesity, Morbid/psychologyABSTRACT
Há alguns relatos na literatura sugerindo associação entre polimorfismos do receptor beta2 -adrenérgico com obesidade e outros com hipertensão arterial. O objetivo do nosso estudo foi estudar a freqüência de um polimorfismo do receptor beta2 adrenérgico (Gln27Glu) em pacientes obesos (BMI 48 + 8,2kg/m 2 ) e relacioná-lo com hipertensão arterial, e níveis de triglicérides, colesterol, insulina e glicose no sangue. Encontramos associação deste polimorfismo em obesos com hipertensão arterial.