Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prader-Willi syndrome is a mental retardation genetic disorder also characterized by hypogonadism, hyperphagia and obesity. We report on a four-years-old boy, born to consanguineous parents, with uncommon co-occurrence of Prader-Willi syndrome, 47,XXY karyotype (Klinefelter syndrome) and coronal craniosynostosis. These are different unrelated conditions and it was not described before in the same patient to the best of our knowledge.
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PMID:Atypical presentation of Prader-Willi syndrome with Klinefelter (XXY karytype) and craniosynostosis. 1679 74

Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 +/- 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.
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PMID:Adrenarche in Prader-Willi syndrome appears not related to insulin sensitivity and serum adiponectin. 1708 44

Prader-Willi syndrome is a rare genetic disorder, affecting 1 out of 25,000 births, in which a critical region of chromosome 15, the 15q11-q13 region, is affected. At birth, PWS infants exhibit severe hypotonia that partially improves, explaining in part suckling and swallowing troubles and the delay in psychomotor development. Characteristic facial features (dysmorphic syndrome) and very small hands and feet are frequently observed at this age. After this initial phase, the most striking signs appear: hyperphagia and absence of satiety often leading to severe obesity in affected children as young as two years. The situation may deteriorate quickly without adequate outside controls and explains in great part the morbidity and mortality of these patients. Other endocrine abnormalities in association with the hypothalamic-pituitary abnormalities contribute to the clinical picture of short stature due to a growth hormone deficiency and incomplete pubertal development. The degree of cognitive dysfunction varies widely from one child to another. It is associated with learning disabilities and impaired speech and language development worsened by psychological and behavioural troubles. The expert consensus is that diagnosis should be based on clinical criteria (Holm's criteria of 1993, revised in 2001) with confirmation by genetic study. Most cases are sporadic and familial cases are rare, those informations should be given as genetic counselling. It is necessary to set up a global and multidisciplinary management. Early diagnosis, early multidisciplinary care and growth hormone treatment have greatly improved the quality of life of these children. We have no long-term data on the effect of GH treatment in adults, on behavioural troubles and autonomy of the persons. In adults, complications particularly linked to obesity and problems of autonomy are still very important.
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PMID:[The Prader-Willi syndrome]. 1749 72

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by an excessive tendency to bone fractures and retarded growth, as well as variable involvement of other connective tissues such as teeth, sclerae, auditory bones and ligaments. A 30-year-old woman (body mass index of 39.6) with OI was scheduled for appendectomy. Because of obesity, abnormal cervical spine mobility and fragile teeth, in addition to the risk of mandibular and facial fractures, general anesthesia including airway management was considered to be difficult and, thus, avoided. Instead, neuraxial blocks were chosen. Although technical difficulty was expected with the blocks as well, epidural and spinal blocks were successfully performed using image intensifier. Neuraxial blocks for patients with skeletal abnormalities in the lumbar spine such as OI have been considered as relative contraindication. However, as described in this case report, these patients, in whom general anesthesia should be avoided, can benefit from neuraxial blocks with the help of image intensifier.
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PMID:[Anesthetic management of an obese patient with osteogenesis imperfecta]. 1757 11

Primary cilium dysfunction underlies the pathogenesis of Bardet-Biedl syndrome (BBS), a genetic disorder whose symptoms include obesity, retinal degeneration, and nephropathy. However, despite the identification of 12 BBS genes, the molecular basis of BBS remains elusive. Here we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium. Interestingly, the BBSome is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Strikingly, Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Conversely, preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish. Our data reveal that BBS may be caused by defects in vesicular transport to the cilium.
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PMID:A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. 1757 16

Prader-Willi syndrome (PWS), a genetic disorder due to an alteration in the paternally derived long arm of chromosome 15, is characterized by a complex clinical picture (short stature, obesity, hypogonadism) that seems to be referable to as a central hypothalamic/pituitary dysfunction. To determine whether there is any diminution in the anterior pituitary gland or other neuroradiological alterations, we retrospectively analysed 91 patients with PWS (42 females, 49 males; age range: 0.7-16.8 years) by cerebral magnetic resonance imaging (MRI). Of these 91 patients, MRI analysis showed a reduction in pituitary height in 45 patients (49.4%), a complete absence of the posterior pituitary bright spot in six patients (6.6%) and other neuroradiological alterations in ten patients (11%). Altogether, neuroradiological alterations were present in 61 of the 91 (67%) patients. Our results indicate that neuroradiological alterations are more frequent in PWS patients than has been reported to date.
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PMID:Pituitary height and neuroradiological alterations in patients with Prader-Labhart-Willi syndrome. 1780 68

Prader-Willi syndrome (PWS) is a complex genetic disorder localized to chromosome 15 and is considered the most common genetic cause of the development of life-threatening obesity. Although some morbidities associated with PWS, including respiratory disturbance/hypoventilation, diabetes, and stroke, are commonly seen in obesity, others such as osteoporosis, growth hormone deficiency, and hypogonadism, and also altered pain threshold and inability to vomit, pose unique issues. Various bariatric procedures have been used to cause gastric stasis, decrease gastric volume, and induce malabsorption, with poor results in PWS patients in comparison with normal obese individuals.
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PMID:Critical analysis of bariatric procedures in Prader-Willi syndrome. 1816 38

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by many features, including obesity and cardiovascular disease. We previously developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect the mechanisms involved in the metabolic disorders associated with BBS, we assessed the development of obesity in these mouse models and found that BBS-null mice were hyperphagic, had low locomotor activity, and had elevated circulating levels of the hormone leptin. The effect of exogenous leptin on body weight and food intake was attenuated in BBS mice, which suggests that leptin resistance may contribute to hyperleptinemia. In other mouse models of obesity, leptin resistance may be selective rather than systemic; although mice became resistant to leptin's anorectic effects, the ability to increase renal sympathetic nerve activity (SNA) was preserved. Although all 3 of the BBS mouse models were similarly resistant to leptin, the sensitivity of renal SNA to leptin was maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently, Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure and a greater reduction in arterial pressure in response to ganglionic blockade. Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons.
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PMID:Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome. 1831 93

Bardet-Biedl syndrome (BBS) is a hereditary disorder whose symptoms include obesity, retinal degeneration, and kidney cysts. Intriguingly, the cellular culprit of BBS seems to lie in the primary cilium, a "cellular antenna" used by a number of signaling pathways. Yet, despite the identification of 12 BBS genes, a consistent molecular pathway for BBS had so far remained elusive. The recent discovery of a stable complex of seven BBS proteins (the BBSome) considerably simplifies the apparent molecular complexity of BBS and provides a clear insight into the molecular basis of BBS. Most tellingly, the BBSome associates with Rabin8, the guanine nucleotide exchange factor for the small GTPase Rab8, and Rab8-GTP enters the primary cilium to promote extension of the ciliary membrane. Thus, BBS is likely caused by defects in vesicular transport to the primary cilium. This chapter describes methods used to purify the BBSome using a tandem affinity purification method and presents a variation of this technique to demonstrate the existence of a stable complex of BBS proteins by sucrose gradient fractionation. When combined with state-of-the art mass spectrometry, these methods can provide a nearly complete BBSome interactome containing factors such as Rabin8.
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PMID:Tandem affinity purification of the BBSome, a critical regulator of Rab8 in ciliogenesis. 1837 85

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous highly heritable disorder which has recently been described to be comorbid in obese subjects. This study investigated phenotype/genotype associations in a consanguineous family with genetic obesity due to the melanocortin-4-receptor (MC4R) (C271R) mutation. MC4R deficiency disrupts hunger/satiety regulation resulting in abnormal eating behaviors. To date, the behavioral/psychiatric characteristics of MC4R deficiency have not been described except for a possible association with Binge Eating Disorder. Twenty-nine subjects of a family known to carry the MC4R (C271R) mutation, were genotyped for the mutation and underwent extensive evaluations in search for physical/psychiatric phenotype characteristics. Subjects originated from proband nuclear families with morbid obese children (BMI percentile > 97%). All probands were homozygous for the MC4R (C271R) mutation. ADHD prevalence was higher than expected only in the groups carrying the homozygous or heterozygous mutation (P = 0.00057, 0.0028, respectively). An obvious difference was observed between the homozygous group and the rest of the family in terms of obesity: homozygous subjects had childhood morbid obesity whereas heterozygous subjects included lean, normal weight and later onset obese subjects. A significant difference was found in ADHD prevalence between the homozygous MC4R (C271R) group (80%) and the rest of the family (22%) (P = 0.033) and a significant trend was found between ADHD prevalence and the number of MC4R (C271R) alleles (P = 0.0267). We conclude that in our sample, the MC4R (C271R) mutation causing obesity, is in association with ADHD. Identifying specific subgroups in which the comorbidity of obesity and ADHD occur may contribute to the understanding of the underlying molecular mechanisms.
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PMID:Attention deficit hyperactivity disorder in obese melanocortin-4-receptor (MC4R) deficient subjects: a newly described expression of MC4R deficiency. 1877 18


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