• Publikační typ
• abstrakt z konference MeSH

Úvod: Monogénová obezita je podmienená mutáciou v jednom z génov zúčastňujúcich sa regulácie leptín-melanokortínovej osi, ktorá hrá dôležitú úlohu v udržiavaní energetickej homeostázy organizmu, najmä v navodzovaní pocitu sýtosti. Cieľ: Cieľom práce je zhrnutie výsledkov DNA analýzy monogénovej obezity u detí od roku 2009 do roku 2015 v laboratóriu DIABGENE. Práca je zameraná najmä na etiológiu a epidemiológiu najčastejších foriem monogénovej obezity u detí na Slovensku. Pacienti a metódy: DNA analýza rôznych génov bola vykonaná doteraz u 565 pacientov s klinickým podozrením na monogénovú obezitu. Podľa literatúry najčastejšie sa vyskytujúci typ monogénovej obezity (v dôsledku mutácií v géne pre melanokortínový receptor 4 – MC4R) bol analyzovaný u 268 detských pacientov so vznikom obezity do 11. roku života, bez špecifickejších klinických príznakov. U pacientov so špecifickejšími príznakmi (endokrinopatie, častý výskyt infekcií, znížený vzrast, ryšavé vlasy, hypokorticizmus a iné) bola vykonaná analýza ďalších génov (SIM1, LEP, LEPR, POMC) spôsobujúcich iné typy monogénovej obezity. Výsledky: V našej štúdii sme našli 2 probandky (0,7 %) s mutáciou v MC4R. Doteraz sme našli jednu mutáciu v SIM1 géne, žiadne sme nenašli v génoch pre LEP, LEPR alebo POMC, čo radí Slovensko medzi krajiny Európy s pravdepodobne najnižším výskytom monogénovej obezity. Záver: Monogénová obezita je zriedkavou príčinou obezity na Slovensku, napriek tomu je vyhľadávanie a diagnostika týchto pacientov dôležité, pretože vyžadujú špecifický manažment ako aj reálnu možnosť kauzálnej liečby v súčasnosti alebo v budúcnosti.

Background: Monogenic obesity is caused by a mutation in on of the genes regulating leptin-melanocortin pathway, which is playing a key role by maintaining energetic homeostasis of organism, mainly inducing a feeling of satiety. Aim: The aim of this work is to conclude results of DNA analysis of monogenic obesity in laboratorium DIABGENE in years 2009–2015. This work is focused on etiology and epidemiology of the most frequent types of monogenic obesity in children. Patients and methods: DNA analysis of varios genes was performed together in 565 patients with a clinical suspicion of monogenic obesity to date. The suggested most frequent type of monogenic obesity (due to a mutation in melanocortin receptor 4 gene – MC4R) was analysed in 268 patients with obesity onset up to 11. years, without other specific clinical signs. In patients with more specific clinical signs (endocrinopathies, infections, decreased growth, red hair, hypocorticism and other) was performed DNA analysis of other genes (SIM1, LEP, LEPR, POMC) causing monogenic obesity. Results: We have found 2 probands (0.7%) with a MC4R mutation in our study. One mutation was found in SIM1 gene and no mutations in LEP, LEPR and POMC gene to date, reffering Slovakia to European countries with probably the lowest prevalence of monogenic obesity. Conclusion: Monogenic obesity is a rare cause of childhood obesity in Slovakia, however searching and diagnosing of these patients is very important, because of the need of specific management as well as real possibility of causal treatment today or in the future.

• MeSH
• časná diagnóza MeSH
• dítě * MeSH
• DNA analýza   MeSH
• gen pro FTO fyziologie   nedostatek   MeSH
• incidence MeSH
• klinické zkoušky jako téma MeSH
• leptinové receptory genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• obezita * genetika   komplikace   MeSH
• prevalence MeSH
• pro-opiomelanokortin genetika   MeSH
• receptor melanokortinový typ 4 analýza   genetika   MeSH
• rizikové faktory MeSH
• Check Tag
• dítě * MeSH
• lidé MeSH
• Geografické názvy
• Slovenská republika MeSH

BACKGROUND: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations. METHODS: The SIM1 promoter region, exons and exon-intron boundaries were sequenced in 126 unrelated obese children and adolescents (2-18 years of age) and 41 adult lean controls of Slovak and Moravian origin. Inclusion criteria for the children and adolescents were a body mass index standard deviation score higher than 2 SD for an appropriate age and sex, and obesity onset at less than 5 years of age. The clinical phenotypes of the SIM1 variant carriers were compared with clinical phenotypes of 4 MC4R variant carriers and with 27 unrelated SIM1 and MC4R mutation negative obese controls that were matched for age and gender. RESULTS: Seven previously described SIM1 variants and one novel heterozygous variant p.D134N were identified. The novel variant was predicted to be pathogenic by 7 in silico software analyses and is located at a highly conserved position of the SIM1 protein. The p.D134N variant was found in an 18 year old female proband (BMI 44.2kg/m2; +7.5 SD), and in 3 obese family members. Regardless of early onset severe obesity, the proband and her brother (age 16 years) did not fulfill the criteria of metabolic syndrome. Moreover, the variant carriers had significantly lower preferences for high sugar (p = 0.02) and low fat, low carbohydrate, high protein (p = 0.02) foods compared to the obese controls. CONCLUSIONS: We have identified a novel SIM1 variant, p.D134N, in 4 obese individuals from a single pedigree which is also associated with lower preference for certain foods.

• MeSH
• detekce genetických nosičů MeSH
• dítě MeSH
• fenotyp MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• nepřímá kalorimetrie MeSH
• obezita etnologie   genetika   MeSH
• předškolní dítě MeSH
• preference v jídle MeSH
• receptor melanokortinový typ 4 genetika   MeSH
• represorové proteiny genetika   MeSH
• rodokmen MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• transkripční faktory bHLH genetika   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika etnologie   MeSH
• Slovenská republika etnologie   MeSH

BACKGROUND: In the present study we aimed: 1) To establish the prevalence and clinical impact of DFNB49 mutations in deaf Roma from 2 Central European countries (Slovakia and Hungary), and 2) to analyze a possible common origin of the c.1331+2T>C mutation among Roma and Pakistani mutation carriers identified in the present and previous studies. METHODS: We sequenced 6 exons of the MARVELD2 gene in a group of 143 unrelated hearing impaired Slovak Roma patients. Simultaneously, we used RFLP to detect the c.1331+2T>C mutation in 85 Hungarian deaf Roma patients, control groups of 702 normal hearing Romanies from both countries and 375 hearing impaired Slovak Caucasians. We analyzed the haplotype using 21 SNPs spanning a 5.34Mb around the mutation c.1331+2T>C. RESULTS: One pathogenic mutation (c.1331+2T>C) was identified in 12 homozygous hearing impaired Roma patients. Allele frequency of this mutation was higher in Hungarian (10%) than in Slovak (3.85%) Roma patients. The identified common haplotype in Roma patients was defined by 18 SNP markers (3.89 Mb). Fourteen common SNPs were also shared among Pakistani and Roma homozygotes. Biallelic mutation carriers suffered from prelingual bilateral moderate to profound sensorineural hearing loss. CONCLUSIONS: We demonstrate different frequencies of the c.1331+2T>C mutation in hearing impaired Romanies from 3 Central European countries. In addition, our results provide support for the hypothesis of a possible common ancestor of the Slovak, Hungarian and Czech Roma as well as Pakistani deaf patients. Testing for the c.1331+2T>C mutation may be recommended in GJB2 negative Roma cases with early-onset sensorineural hearing loss.

• MeSH
• alely MeSH
• efekt zakladatele MeSH
• exony genetika   MeSH
• frekvence genu MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kojenec MeSH
• lidé MeSH
• MARVELD2 protein genetika   MeSH
• mutace * MeSH
• nedoslýchavost vrozené   etnologie   genetika   MeSH
• prevalence MeSH
• Romové genetika   MeSH
• sekvenční homologie nukleových kyselin MeSH
• věk při počátku nemoci MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Maďarsko MeSH
• Pákistán MeSH
• Slovenská republika MeSH