Browsing by Subject "hyperphagia"

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  • Loid, Petra; Mäkitie, Riikka; Costantini, Alice; Viljakainen, Heli; Pekkinen, Minna; Mäkitie, Outi (2018)
    The genetic background of severe early-onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early-onset obesity and variable intellectual disability. Myelin-transcriptor-factor-1-like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13-year-old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z-score +2.3) and obesity at 2 years of age (BMI Z-score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development. He also had speech delay, strabismus, hyperactivity and intellectual disability. Brain MRI was normal. The parents and sister had normal BMI. Whole-genome sequencing identified in the index patient a novel de novo frameshift deletion that introduces a premature termination of translation NM_015025.2(MYT1L): c.2215_2224delACGCGCTGCC, p.(Thr739Alafs*7) in MYT1L. The frameshift variant was confirmed by Sanger sequencing. Our finding supports the association of MYT1L mutations with early-onset syndromic obesity. The identification of novel monogenic forms of childhood-onset obesity will provide insights to the involved genetic and biologic pathways.
  • Loid, Petra; Mustila, Taina; Mäkitie, Riikka E.; Viljakainen, Heli; Kämpe, Anders; Tossavainen, Päivi; Lipsanen-Nyman, Marita; Pekkinen, Minna; Mäkitie, Outi (2020)
    Context: The hypothalamic circuit has an essential role in the regulation of appetite and energy expenditure. Pathogenic variants in genes involved in the hypothalamic leptin-melanocortin pathway, including melanocortin-4-receptor (MC4R), have been associated with monogenic obesity. Objective: To determine the rate and spectrum of rare variants in genes involved in melanocortin pathway or hypothalamic development in patients with severe early-onset obesity (height-adjusted weight >60% before age 10 years). Methods: We used a custom-made targeted exome sequencing panel to assess peripheral blood DNA samples for rare (minor allele frequency Results: We identified a novel frameshift deletion in MC4R (p.V103Afs5*) in two unrelated patients and a previously reported MC4R variant (p.T112M) in one patient. In addition, we identified rare heterozygous missense variants in ADCY3 (p.G1110R), MYT1L (p.R807Q), ISL1 (p.I347F), LRP2 (p.R2479I, and p.N3315S) and a hemizygous missense variant in GRPR (p.L87M) (each in one patient), possibly contributing to the obesity phenotype in these patients. Altogether 8 % (7/92) of the subjects had rare pathogenic/likely pathogenic variants in the studied genes. Conclusions: Rare genetic variants within the hypothalamic circuit are prevalent and contribute to the development of severe early-onset obesity. Targeted exome sequencing is useful in identifying affected subjects. Further studies are needed to evaluate the variants' clinical significance and to define optimal treatment.
  • Koski, M.; Naukkarinen, H. (2017)
    Background: Obesity has a multifaceted etiology that involves genetic, biological and behavioral factors, body growth, eating habits, energy expenditure and the function of adipose tissue. The present study aimed to expand upon knowledge about the relationships among obesity, emotions and eating habits in severely obese individuals using a case-control method. Methods: The subject group consisted of 112 individuals (81 females and 31 males) receiving a permanent disability pension primarily for obesity. The control subjects were randomly selected from the same area and were receiving a disability pension for a different primary illness. The controls were matched with the subjects by the place of residence, sex, age, the time since the pension was granted and occupation. Psychiatric interviews were conducted on all participants. The results were analyzed using the chi-squared test (X2-test) and the percent distribution. The subject and control groups were compared using the t-test for paired variables. Conditional logistic regression analysis was also conducted. Results: The emotional state of eating was significantly associated with quarrels and feelings of loneliness. The subjects suffered from night eating syndrome, which was associated with an increased risk of early retirement. Binge eating syndrome was observed more frequently in the study group. The subjects reported feeling increased hunger compared with the controls. A significant percentage of the subjects had a body mass index of≥40. No differences in eating habits were observed between the groups. Conclusion: This study provides information on the relationship between emotions and eating habits in obesity, which is a rarely studied topic. We believe that our study provides a novel and necessary overview of the associations among severe obesity, emotions and eating habits. © The Author(s).