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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Prader-Willi (PWS) and Angelman syndromes (AS) share the same apparent cytogenetic and molecular lesions of 15q11-13 and yet exhibit distinct clinical phenotypes. The etiology of PWS or AS appears to depend on the parental origin of the aberrant chromosome 15. Substantial clinical overlap has not been reported between deletion-positive PWS and AS patients. In the present study, we report the clinical, cytogenetic, and molecular findings in three AS patients. The first patient is a mentally retarded woman with a visible deletion of 15q11-13 with typical craniofacial, behavioral, and neurologic changes of AS. This patient is hyperphagic, and she is moderately obese for her height. Her hands and feet are small. These manifestations are more characteristic of PWS and not of AS. The molecular studies showed deletions of maternal origin for five distal PWCR loci. The most proximal locus, D15S18, was not deleted. These findings are identical to those found in our third AS patient who does not have any PWS features. To the best of our knowledge, this is the first report of concurrence of hyperphagia with consequent obesity and the AS phenotype in a patient with a del 15(q11-13) of maternal origin. These clinical findings suggest that overlap in the symptoms of PWS and AS can occur. Our second AS patient presents with atypical molecular findings in that he cannot be classed into any of the three proposed sub-groups of AS patients and may be representative of a fourth sub-group of AS patients.
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PMID:Molecular and clinical overlap of Angelman and Prader-Willi syndrome phenotypes. 168 91

Characteristics are hypotonia, problems with feeding and thriving in the neonate and infant, later hyperphagia and severe obesity. Other findings are dysmorphic traits, hypogonadism, short stature, developmental delay, mental retardation and behavioural problems. Diabetes mellitus (NIDDM) is frequent in adults. Treatment is symptomatic. Prognosis is determined by obesity. PWS occurs almost always sporadically and is found in all ethnic groups and in both sexes. The epidemiology of PWS in Denmark is unknown. In 95% of cases with PWS cytogenetic and molecular genetic investigations show either deletion of the paternal chromosome 15q11q13 or uniparental maternal disomy of chromosome 15. Since 1992 150 bloodsamples of patients suspected for PWS have been investigated by cytogenetic and molecular genetic techniques at the John F. Kennedy Institute, DK-2600 Glostrup; deletion of the paternal chromosome 15 was found in 15 and uniparental maternal disomy of chromosome 15 in eight cases.
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PMID:[Prader-Willi syndrome--clinical picture and genetics]. 772 49

Prader-(Labhart-)Willi syndrome (PWS) is characterized by infantile hypotonia, early childhood obesity, mental deficiency, short stature, small hands and feet and hypogonadism. In 70% of the cases this syndrome is associated with a defect of chromosome 15 at 15q11-q13, close to the location of the 7B2 gene (15q13-q14). The majority of the remaining PWS patients display maternal uniparental disomy on chromosome 15. Since the 7B2 gene products are expressed in neuroendocrine cells that are probably affected in PWS, e.g. by a pleiotrophic influence of the neighboring deletion, the presence of 7B2 was studied in the supraoptic and paraventricular nucleus of the hypothalamus of five subjects clinically diagnosed as PWS patients using five antibodies against various parts of the 7B2 precursor polypeptide. Three of the five PWS patients studied showed no reaction to the 7B2 antibody MON-102, whereas all 30 control patients did. However, one of the three MON-102 non-reacting PWS patients reacted to other 7B2 antibodies. In conclusion, the vanishing of 7B2 gene products is not obligatory for PWS, possibly due to the variable genetic background of PWS patients. However, in most patients there is a clear modification of 7B2 expression, pointing to altered neuroendocrine functions.
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PMID:Differential expression of the neuroendocrine polypeptide 7B2 in hypothalami of Prader-(Labhart)-Willi syndrome patients. 782 Jun 29

Basal IGF-I levels and the GH response to at least two among provocative stimuli such as clonidine (CLO, Catapresan, 150 mcg/m2 p.o.), GHRH (1 mcg/kg i.v.)+arginine (ARG, 0.5 g/kg i.v. infusion during 30 min) and GHRH+pyridostigmine (PD, Mestinon cpr 60 mg p.o.) have been evaluated in 43 children with Prader-Willi syndrome (PWS, 17 males and 26 females, age 3-22 yr, 7 normal weight and 36 obese PWS), in 25 normal short children (NC, 17 males and 8 females, 7.7-18.5 yr) and in 24 children with simple obesity (OB, 14 males, 10 females, 7.7-21.5 yr). Both normal weight and obese PWS had mean IGF-I levels lower than those recorded in NC (p<0.001) and OB (p<0.001). The GH responses to GHRH+ARG and GHRH+PD in NC were similar and higher than that to CLO (p<0.001). In PWS the GH response to GHRH+ARG was higher than that to GHRH+PD (p<0.001) which, in turn, was higher than that to CLO (p<0.001); these responses in PWS were lower than those in normal children (p<0.02) and similar to those in OB. In normal weight PWS the GH responses to GHRH+ARG and to GHRH+PD were similar and higher than to CLO (p<0.05); however, each provocative stimulus elicited a GH rise lower than that in NC (p<0.05). In obese PWS as well as in OB the GH response to GHRH+ARG was higher than that to GHRH+PD (p<0.02) which, in turn, was higher than that to CLO (p<0.001); all GH responses in obese PWS and OB were lower than those in NC (p<0.001) but similar to those in normal weight PWS. In conclusion, patients with PWS show clear reduction of IGF-I levels as well as of the somatotroph responsiveness to provocative stimuli independently of body weight excess. These results strengthen the hypothesis that PWS syndrome is frequently connotated by GH insufficiency.
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PMID:GH/IGF-I axis in Prader-Willi syndrome: evaluation of IGF-I levels and of the somatotroph responsiveness to various provocative stimuli. Genetic Obesity Study Group of Italian Society of Pediatric Endocrinology and Diabetology. 1080 Jul 60

Ghrelin is a 28-amino acid peptide recently identified in the stomach as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Ghrelin is a potent stimulator of GH secretion. It was recently shown that circulating ghrelin levels in humans rise shortly before and fall shortly after every meal, and that ghrelin administration increases voluntary food intake. The hypothesis that ghrelin hypersecretion might contribute to genetic obesity has never been investigated. In this context, Prader-Willi syndrome is the most common form of human syndromic obesity. As ghrelin affects appetite as well as GH secretion and both are abnormal in PWS, it has been surmised that these alterations might be due to ghrelin dysregulation. The aim of the study was to investigate whether ghrelin is suppressed by the meals differently in PWS children than in PWS adults. Overnight circulating fasting ghrelin levels and ghrelin levels 120 min after breakfast were assayed in 7 PWS children (10.2 +/- 1.7 yr), 7 subjects with morbid obesity (10.3 +/- 1.3 yr), and 5 normal controls (8.4 +/- 1.4 yr). Because of the data spread, no statistical difference was observed in fasting ghrelin levels between PWS and control children (p = NS); anyway, fasting ghrelin levels were significantly lower in obese children than in the other groups (p < 0.05 vs. control and PWS children). Ghrelin levels were slightly suppressed by the meal in control subjects (mean fasting ghrelin: 160.2 +/- 82 pg/ml; after the meal, 141.2 +/- 57 pg/ml, p = NS); the meal failed to suppress ghrelin levels in obese children (mean fasting ghrelin: 126.4 +/- 8.5 pg/ml; after the meal, 119.1 +/- 8.3 pg/ml, p = NS). Interestingly, the meal markedly suppressed ghrelin levels in PWS children (mean fasting ghrelin: 229.5 +/- 70.4 pg/ml; after the meal, 155.8 +/- 34.2 pg/ml, p < 0.01). In conclusion, since a lack of decrease in circulating ghrelin induced by the meal was previously reported in PWS adults, the finding of a meal-induced decrease in ghrelin levels in our population of young PWS would imply that the regulation of the ghrelin system involved in the orexigenic effects of the peptide is operative during childhood, although it progressively deteriorates and is absent in adulthood when hyperphagia and obesity progressively worsen.
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PMID:Maintenance of a normal meal-induced decrease in plasma ghrelin levels in children with Prader-Willi syndrome. 1505 69

The association of obesity, phenotypic abnormalities and mental retardation characterizes syndromic obesity. Its most common form is the Prader-Willi syndrome (PWS-- neonatal hypotonia, poor sucking, delayed psychomotor development, hyperphagia, severe obesity, short stature, small hands and feet, hypogonadism, mild to moderate mental retardation and behavioral disorders). A PWS-like phenotype has been described in patients with chromosome abnormalities involving the chromosome region 6q16.2 that includes the SIM1 gene. Herein we report cytogenetic and gene studies including a screening for the SIM1 gene deletion, performed on 87 patients with PWS-like phenotype, and describe the fifth case of syndromic obesity with an interstitial deletion of the chromosome segment 6q16-q21 and suggest that mutational analysis and further studies of the parental origin of chromosome alterations of 6q16.2 in patients with and without PWS-like phenotype are needed to evaluate possible imprinting effects of SIM1 gene and establish the contribution that alterations in this gene makes to the etiology of syndromic and non-syndromic obesity.
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PMID:A new case of interstitial 6q16.2 deletion in a patient with Prader-Willi-like phenotype and investigation of SIM1 gene deletion in 87 patients with syndromic obesity. 1682 51

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

Prader-Willi syndrome (PWS [MIM 176270]) is a neurogenetic disorder characterized by decreased fetal activity, muscular hypotonia, failure to thrive, short stature, obesity, mental retardation, and hypogonadotropic hypogonadism. It is caused by the loss of function of one or more imprinted, paternally expressed genes on the proximal long arm of chromosome 15. Several potential PWS mouse models involving the orthologous region on chromosome 7C exist. Based on the analysis of deletions in the mouse and gene expression in PWS patients with chromosomal translocations, a critical region (PWScr) for neonatal lethality, failure to thrive, and growth retardation was narrowed to the locus containing a cluster of neuronally expressed MBII-85 small nucleolar RNA (snoRNA) genes. Here, we report the deletion of PWScr. Mice carrying the maternally inherited allele (PWScr(m-/p+)) are indistinguishable from wild-type littermates. All those with the paternally inherited allele (PWScr(m+/p-)) consistently display postnatal growth retardation, with about 15% postnatal lethality in C57BL/6, but not FVB/N crosses. This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype.
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PMID:Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation. 1816 85

The term "imprinted gene" refers to genes whose expression is conditioned by their parental origin. Among theories to unravel the evolution of genomic imprinting, the kinship theory prevails as the most widely accepted, because it sheds light on many aspects of the biology of imprinted genes. While most assumptions underlying this theory have not escaped scrutiny, one remains overlooked: mothers are the only source of parental investment in mammals. But, is it reasonable to assume that fathers' contribution of resources is negligible? It is not in some key mammalian orders including humans. In this research, I generalize the kinship theory of genomic imprinting beyond maternal contribution only. In addition to deriving new conditions for the evolution of imprinting, I have found that the same gene may show the opposite pattern of expression when the investment of one parent relative to the investment of the other changes; the reversion, interestingly, does not require that fathers contribute more resources than mothers. This exciting outcome underscores the intimate connection between the kinship theory and the social structure of the organism considered. Finally, the insight gained from my model enabled me to explain the clinical phenotype of Prader-Willi syndrome. This syndrome is caused by the paternal inheritance of a deletion of the PWS/AS cluster of imprinted genes in human Chromosome 15. As such, children suffering from this syndrome exhibit a striking biphasic phenotype characterized by poor sucking and reduced weight before weaning but by voracious appetite and obesity after weaning. Interest in providing an evolutionary explanation to such phenotype is 2-fold. On the one hand, the kinship theory has been doubted as being able to explain the symptoms of patients with Prader-Willi. On the other hand, the post-weaning symptoms remain as one of the primary concern of pediatricians treating children with Prader-Willi. In this research, I reconcile the clinical phenotype of Prader-Willi syndrome with the kinship theory, contending that paternal investment relative to maternal investment increases after weaning. I also propose a genetic composition of the PWS/AS cluster, discuss the effects of new types of mutations, and contemplate the potential side effects of reactivating silent genes for medical purposes.
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PMID:Evolution of genomic imprinting with biparental care: implications for Prader-Willi and Angelman syndromes. 1875 49

As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.
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PMID:Early childhood obesity is associated with compromised cerebellar development. 1943 3


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