Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
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Heves Kırmızıbekmez
,
Yasemin Kendir Demirkol
,
Özlem Akgün Doğan
,
Gülcan Seymen
Abstract
Objectives
Genetic factors have a key role in childhood obesity with higher rates in children than adults. Among the monogenic types of non-syndromic obesity, melanocortin-4 receptor (MC4R) deficiency is the most frequent cause. Beside pathogenic variants, single-nucleotide polymorphisms in MC4R gene are also associated with lower energy expenditure. The aim of this study was to estimate the frequency of MC4R variants and polymorphisms in a cohort of Turkish children and adolescents with severe early-onset obesity, and to understand the clinical features of patients.
Methods
Patients, 1–17 years of age, with the onset of obesity before 10 years of age and a body mass index (BMI) standard deviation score (SDS) of >2.3, and who had a family history of early-onset obesity in at least one of their first-degree relatives were included in the study. Beside routine blood tests genetic analyses for MC4R gene were performed.
Results
Analyses of MC4R revealed previously known variations in three (3.5%) patients, and pathogenic polymorphisms related with obesity in four (4.7%) patients. BMI SDS values were between 2.8 and 5.5 SDS in the pathogenic variant carrier group, and 2.8–4.9 SDS in the polymorphism group. Mean BMI SDS in variant-negative group was 3.4 ± 0.82.
Conclusions
Investigation of the MC4R in individuals with early-onset obesity and presence of obesity first-degree relatives is important. Hypertension is a rare comorbidity compared to other causes. Contrary to studies reporting that insulin resistance was absent or very rare, we found it as a frequent finding in both pathogenic variants and polymorphisms of MC4R.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
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© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
Articles in the same Issue
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
