Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics

Basit Öğe Kaydı
dc.contributor.authorAykut, Ayca
dc.contributor.authorozen, Samim
dc.contributor.authorGoksen, Damla
dc.contributor.authorAta, Aysun
dc.contributor.authorOnay, Huseyin
dc.contributor.authorAtik, Tahir
dc.contributor.authorÖzkınay, Ferda
dc.date.accessioned2020-12-01T12:01:59Z
dc.date.available2020-12-01T12:01:59Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractMelanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. the autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of >= 95th percentile, and as extreme obesity is defined if the BMI >= 120% of the 95th percentile or >= 35 kg/m(2). Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. the mean age of the patients was 7.3 +/- 3.7 years, and the mean BMI SDS was 3.7 +/- 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing. Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. in such patients, comorbidities of obesity can be seen from early years.What is known center dot the frequency of MC4R mutations in obese patients was approximately 0-6.3%.What is new center dot in obese Turkish pediatric population, unlike other European countries, MC4R gene variants are quite common as we found a variant rate of 8.6%center dot We believe it is necessary to screen the variants in MC4R gene in patients with severe childhood-onset obesity and who had early-onset obesity in at least one of their first-degree relatives in Turkish population.en_US
dc.description.sponsorshipEge University Faculty of MedicineEge Universityen_US
dc.description.sponsorshipEge University Faculty of Medicineen_US
dc.identifier.doi10.1007/s00431-020-03630-7en_US
dc.identifier.endpage1452en_US
dc.identifier.issn0340-6199
dc.identifier.issn1432-1076
dc.identifier.issue9en_US
dc.identifier.pmid32185475en_US
dc.identifier.scopus2-s2.0-85082793686en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1445en_US
dc.identifier.urihttps://doi.org/10.1007/s00431-020-03630-7
dc.identifier.urihttps://hdl.handle.net/11454/62570
dc.identifier.volume179en_US
dc.identifier.wosWOS:000520655700001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofEuropean Journal of Pediatricsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectMonogenic obesityen_US
dc.subjectPediatricsen_US
dc.subjectMC4Ren_US
dc.titleMelanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristicsen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu