1/28. Interstitial 6q deletion with a Prader-Willi-like phenotype: a new case and review of the literature.We report on an additional fourth case of Prader-Willi (PW)-like phenotype and an interstitial deletion of 6q. Despite sharing clinical characteristics, patients with a PW-like phenotype and a deletion of 6q, have features which distinguish them from prader-willi syndrome (PWS) patients. This case emphasizes the need to examine patients with suspected PWS, but who are negative for recognizable deletions of 15q11-q13 or uniparental maternal disomy of chromosome 15, for a deletion of 6q.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
2/28. congenital hypothyroidism with prader-willi syndrome.We report a 1 year-old female patient with severe hypotonia who has congenital hypothyroidism and prader-willi syndrome (PWS). At birth she was found to have congenital hypothyroidism caused by an ectopic sublingual thyroid gland and was commenced on thyroid replacement therapy. She continued to have severe motor delay and therefore further diagnostic evaluation was performed. PWS was confirmed by dna and fluorescence in situ hybridization (FISH) analysis. This report emphasizes the need to further investigate patients who are found to have congenital hypothyroidism and do not improve adequately on treatment.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
3/28. Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes.Although uniparental disomy often results from the postzygotic rescue of a meiotic non-disjunction event, mosaicism is usually confined to the placenta. We describe a girl with prader-willi syndrome (PWS) who is mosaic for normal cells and cells with maternal uniparental disomy 15 [upd(15)mat] in blood and skin. Somatic mosaicism was confirmed by cloning and genotyping of skin fibroblasts. X inactivation studies indicated that upd occurred prior to X inactivation. rna samples from the cloned cells were used in dna microarray experiments to study the effect of upd(15)mat on the gene expression pattern of fibroblasts. Proof of principle was obtained by detecting several chromosome 15 genes known to be imprinted. We did not obtain any evidence for novel 15q genes showing imprinted expression in fibroblasts. Differentially expressed genes on other chromosomes are candidates for downstream genes regulated by an imprinted gene and may play a role in the pathogenesis of PWS. The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin ii (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits.- - - - - - - - - - ranking = 1.6782024793388keywords = sample (Clic here for more details about this article) |
4/28. Unexpected death and critical illness in prader-willi syndrome: report of ten individuals.Individuals with prader-willi syndrome (PWS) generally survive into adulthood. Common causes of death are obesity related cor pulmonale and respiratory failure. We report on a case series of eight children and two adults with unexpected death or critical illness. Our data show age-specific characteristics of PWS patients with fatal or life-threatening illnesses. Under the age of 2 years, childhood illnesses in general were associated with high fever and rapid demise or near-demise. Hypothalamic dysfunction likely plays a role in exaggerated fever response, but also perhaps in central regulation of adrenal function. Below average sized adrenal glands were found in three children, which raises the possibility of unrecognized adrenal insufficiency in a subset of individuals with PWS and emphasizes the vital role of autopsy. The tub drowning death of an adult patient could be related to central hypersomnia, which has been reported in PWS. We suggest that increased risk for critical illness be considered in the discussion of anticipatory guidance for the care of infants with PWS. Since a number of children died while hospitalized, particularly close observation of PWS children who are ill enough to warrant hospital admission is recommended.- - - - - - - - - - ranking = 2keywords = size (Clic here for more details about this article) |
5/28. Boy with 47,XXY,del(15)(q11.2q13) karyotype and prader-willi syndrome: a new case and review of the literature.We report on a 10-year-old boy with a 47,XXY,del(15)(q11.2q13) karyotype and a prader-willi syndrome phenotype. His medical history and physical examination conformed to all of the major clinical criteria for prader-willi syndrome, but his height was taller than expected based on his hand and foot sizes. The deleted chromosome 15 was paternal in origin and molecular analysis showed maternal origin for the additional x chromosome. These findings suggest that the presence of these two disorders was coincidental in our patient. This supports the findings in the two other 47,XXY and Prader-Willi cases for which parent of origin studies have been published. Given the information from the literature and presented herein, we suggest that genetic counseling for cases of PWS and 47,XXY should address these two conditions separately.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
6/28. Maternal UPD(14) in the patient with a normal karyotype: clinical report and a systematic search for cases in samples sent for testing for prader-willi syndrome.Maternal uniparental disomy for chromosome 14 causes a recognizable phenotype that has a number of consistent features, irrespective of the underlying chromosome abnormality. To illustrate this, we describe a patient with a 46,XX karyotype whose short stature, hypotonia, feeding problems, truncal obesity, early puberty, learning difficulties, and craniofacial characteristics led to a diagnosis of maternal (mat) UPD(14). No evidence is available to indicate how common mat UPD(14) in patients with a normal karyotype might be. Because of the similarity between prader-willi syndrome (PWS) and the mat UPD(14) phenotype in childhood, we systematically tested samples from 35 patients with normal karyotypes and an unexplained PWS-like phenotype referred to the Wessex genetics Service. We sought to address the practical question should laboratories carry out tests for mat UPD(14) on all samples received for PWS testing when PWS testing gives negative results? None of the samples tested showed evidence of mat UPD(14). Routine screening of dna from patients with possible PWS cannot be recommended on this basis.- - - - - - - - - - ranking = 11.747417355372keywords = sample (Clic here for more details about this article) |
7/28. diabetic ketoacidosis secondary to growth hormone treatment in a boy with prader-willi syndrome and steatohepatitis.A 13 year-old boy with prader-willi syndrome and steatohepatitis presented with diabetic ketoacidosis 4 weeks after the initiation of growth hormone (GH) treatment. He did not have signs or symptoms of type 2 diabetes mellitus (DM2) before the initiation of GH treatment. hyperglycemia resolved 2 months after discontinuation of GH. He redeveloped DM2 6 months later associated with excessive weight gain. diabetic ketoacidosis as a rare complication of GH therapy emphasizes the importance of screening for carbohydrate intolerance before and during GH treatment in patients with prader-willi syndrome. Steatohepatitis may be the only manifestation of insulin resistance and warrants further evaluation.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
8/28. prader-willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization.prader-willi syndrome (PWS) is caused by lack of expression of paternally inherited genes on chromosome 15q11-->15q13. Most cases result from microdeletions in proximal chromosome 15q. The remainder results from maternal uniparental disomy of chromosome 15, imprinting center defects, and rarely from balanced or unbalanced chromosome rearrangements involving chromosome 15. We report a patient with multiple congenital anomalies, including craniofacial dysmorphology, microcephaly, bilateral cryptorchidism, and developmental delay. cytogenetic analysis showed a de novo 45,XY,der(5)t(5;15)(p15.2;q13), -15 karyotype. In effect, the proband had monosomies of 5p15.2-->pter and 15pter-->15q13. methylation polymerase chain reaction analysis of the promoter region of the SNRPN gene showed only the maternal allele, consistent with the PWS phenotype. The proband's expanded phenotype was similar to other patients who have PWS as a result of unbalanced translocations and likely reflects the contribution of the associated monosomy. Array comparative genomic hybridization (array CGH) confirmed deletions of both distal 5p and proximal 15q and provided more accurate information as to the size of the deletions and the molecular breakpoints. This case illustrates the utility of array CGH in characterizing complex constitutional structural chromosome abnormalities at the molecular level.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
9/28. A neuropathological study of a case of the prader-willi syndrome with an interstitial deletion of the proximal long arm of chromosome 15.An autopsy case, a 6-month-old girl, with an interstitial deletion of the long arm of chromosome 15;del(15)(q11.1q12) was reported. muscle hypotonia, poor sucking and intermittent ocular deviation were noticed soon after birth. She also exhibited external features peculiar to the prader-willi syndrome (PWS). The muscle hypotonia persisted and head control was not achieved. She died at the age of 6 months due to bronchopneumonia. G-banding analysis of prometaphase chromosomes revealed a deletion of chromosome 15. bronchopneumonia of the lungs and fatty metamorphosis of the liver were found. Neuropathological anomalies recognized were; disturbed undulating structures, resembling cortical micropolygyria and pachygyria, in the dentate nucleus and the inferior olivary nucleus, grumose degeneration of the nerve cells in the dentate nucleus, and heterotopia of middle-sized neurons in the cerebellar white matter. No abnormalities were observed in the hypothalamus-pituitary system. In some autopsy cases of PWS, cerebellar lesions have been reported. These might be related to the muscle hypotonia in PWS.- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
10/28. Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: specific regions, extent of deletions, parental origin, and clinical consequences.It has recently been shown that apparently similar deletions of chromosome 15q occur commonly in the Prader-Willi and Angelman syndromes. The distinctness of the syndromes suggests that the deletions are not identical. To address this possibility, the specific bands involved and the sizes of the deletions were compared in seven patients with prader-willi syndrome and 10 patients with angelman syndrome using high-resolution G-, Q-, and fluorescent R-banding techniques. The parental origin of the nine cases of angelman syndrome for which parents were available for study was determined. The same proximal band was deleted (q11.2) in both syndromes. In general, the deletion in patients with angelman syndrome was larger, though variable, and included bands q12 and part of q13. All of the studied deletions in patients with angelman syndrome were of maternal origin. This contrasts with the predominant paternal origin of the deletion in patients with prader-willi syndrome. Two possible reasons for these observations are postulated: 1) the deleted regions are different at the cytologic and/or molecular level because of different exchange points in meiosis in males and females or to different mechanisms of breakage in males and females, resulting in differing breakpoints; 2) the deleted regions are essentially the same, but differential expression of the genes in the homologous chromosome 15 has occurred (imprinting).- - - - - - - - - - ranking = 1keywords = size (Clic here for more details about this article) |
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