1/187. Syndromal obesity due to paternal duplication 6(q24.3-q27).The likelihood of a paternally expressing imprinted gene in chromosome region 6(q23-24) has been highlighted by cases of transient neonatal diabetes mellitus (TNDM) in which paternal uniparental disomy (UPD) for chromosome 6 or paternal duplication 6(q23-qter) was detected. We present the case of a 38-year-old man with moderate to severe intellectual delay, short stature, small hands and feet, eye abnormality, small mouth, and obesity (without hyperphagia) beginning in mid-childhood. The perinatal and neonatal histories were normal. The patient had a duplication within 6q. fluorescence in situ hybrisation studies were performed with single and dual hybridisations using a chromosome 6 library probe, short and long arm subregional probes, 6q23-24, 6q25.3-6qter locus-specific probes, and a 6q telomere probe. The hybridisation results defined an inverted duplication of 6q24.3 to 6q27. DNA studies with microsatellite markers from 6p and 6q showed regular biparental inheritance of chromosome 6 and confirmed that the duplication was paternal in origin. Our patient appears to be the first one known to have paternal duplication of chromosome area 6(q24-q27) who did not have TNDM as an infant. He has remained nondiabetic, although obesity, without hyperphagia, has been a constant problem since its onset in mid-childhood.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
2/187. Genetic factors in human sleep disorders with special reference to Norrie disease, prader-willi syndrome and Moebius syndrome.Sleep-wake problems are common in specific inborn errors of metabolism and structure of the central nervous system. Psychological factors, behavioural difficulties, metabolic disturbances, and widespread rather than focal damage to the nervous system are present in many of these diseases and all influence the sleep-wake cycle. However, a number of conditions cause relatively focal damage to the neuroanatomical substrate of sleeping and waking. These include fatal familial insomnia, with involvement of the prion protein gene on chromosome 20, Norrie disease, the prader-willi syndrome and the Moebius syndrome. The last three important conditions, although rare, are considered in detail in this review. They result in sensory deprivation, hypothalamic and mid-brain damage, and involve the X-chromosome, chromosome 15, and chromosome 13, respectively. These conditions cause a wide variety of sleep disturbance, including parasomnias, daytime sleepiness, and a condition like cataplexy. The place of the relevant gene products in normal sleep regulation needs further exploration.- - - - - - - - - - ranking = 0.8keywords = chromosome (Clic here for more details about this article) |
3/187. Duplication within chromosome region 15q11-q13 in a patient with similarities to prader-willi syndrome confirmed by region-specific and band-specific fish.We report on a patient presenting with mental retardation and obesity and a proximal duplication of chromosome 15. The patient shared some clinical signs with prader-willi syndrome. With a region-specific paint, generated by microdissection, a duplication in region 15q11.2-q13 was shown to be present. Subsequently, FISH with probes localized to chromosome region 15q11.2-q12 and microsatellite analysis was used to characterize this chromosome aberration further and an insertion duplication within the region frequently deleted in Prader-Willi and angelman syndrome was demonstrated.- - - - - - - - - - ranking = 1.4keywords = chromosome (Clic here for more details about this article) |
4/187. Maternal uniparental disomy for chromosome 14 in a boy with a normal karyotype.We report on a boy with a maternal uniparental disomy for chromosome 14 (UPD(14)). At 7 years of age he was referred to us by the paediatrician because of symptoms of prader-willi syndrome (PWS). He showed short stature, obesity, mild developmental delay, cryptorchidism, and some mild dysmorphic features. The history further indicated intrauterine growth retardation at the end of the pregnancy. His mother was 44 years of age at the time of his birth. After birth he showed hypotonia with poor sucking, for which gavage feeding was needed. Motor development was delayed. After 1 year he became obese despite a normal appetite. Recurrent middle ear infections, a high pain threshold, and a great skill with jigsaw puzzles were reported. There were no behavioural problems or sleep disturbance. Chromosomal analysis was normal (46,XY). DNA analysis for prader-willi syndrome showed no abnormalities. Two years later he was re-examined because we thought his features fitted the PWS-like phenotype associated with maternal UPD(14). At that time precocious puberty was evident. DNA analysis showed maternal heterodisomy for chromosome 14. In all the previously described 11 cases with maternal UPD(14), a Robertsonian translocation involving chromosome 14 was detected cytogenetically before DNA analysis. This is the first report of diagnosis of maternal UPD(14) based on clinical features. This finding underlines the importance of DNA analysis for maternal UPD(14) in patients with a similar PWS-like phenotype even without previous identification of a Robertsonian translocation involving chromosome 14.- - - - - - - - - - ranking = 1.6keywords = chromosome (Clic here for more details about this article) |
5/187. prader-willi syndrome in a child with XYY.We report a 26-month-old boy with XYY syndrome, with the complication of prader-willi syndrome (PWS) due to uniparental maternal disomy of chromosome 15. To our knowledge, this is the first case of XYY syndrome and PWS. Clinical findings were fully compatible with the diagnostic criteria for PWS. Molecular analysis revealed a maternal heterodisomy of chromosome 15, indicating that non-disjunction of chromosome 15 had occurred at maternal meiosis I, and that the non-disjunction of chromosome Y and of chromosome 15 had occurred independently.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
6/187. 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 = 0.20010696689669keywords = chromosome, ring (Clic here for more details about this article) |
7/187. Submicroscopic deletion in cousins with prader-willi syndrome causes a grandmatrilineal inheritance pattern: effects of imprinting.The prader-willi syndrome (PWS) critical region on 15q11-q13 is subject to imprinting. PWS becomes apparent when genes on the paternally inherited chromosome are not expressed. Familial PWS is rare. We report on a family in which a male and a female paternal first cousin both have PWS with cytogenetically normal karyotypes. fluorescence in situ hybridization (FISH) analysis shows a submicroscopic deletion of SNRPN, but not the closely associated loci D15S10, D15S11, D15S63, and GABRB3. The cousins' fathers and two paternal aunts have the same deletion and are clinically normal. The grandmother of the cousins is deceased and not available for study, and their grandfather is not deleted for SNRPN. dna methylation analysis of D15S63 is consistent with an abnormality of the imprinting center associated with PWS. "Grandmatrilineal" inheritance occurs when a woman with deletion of an imprinted, paternally expressed gene is at risk of having affected grandchildren through her sons. In this case, PWS does not become evident as long as the deletion is passed through the matrilineal line. This represents a unique inheritance pattern due to imprinting.- - - - - - - - - - ranking = 0.2keywords = chromosome (Clic here for more details about this article) |
8/187. Third prader-willi syndrome phenotype due to maternal uniparental disomy 15 with mosaic trisomy 15.We report on a boy with mosaicism for trisomy 15 and prader-willi syndrome (PWS) due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS and trisomy 15 mosaicism. Although our patient is unusual in having maternal isodisomy rather than the more common maternal heterodisomy, we think that his more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to homozygosity for deleterious chromosome 15 genes. We propose that individuals with PWS have one of three similar but distinctive phenotypes depending on the cause of their condition. patients with paternal deletions have the typical PWS phenotype, patients with maternal UPD have a slightly milder phenotype with better cognitive function, and those with maternal UPD and mosaic trisomy 15 have the most severe phenotype with a high incidence of congenital heart disease. These phenotype-genotype differences are useful to guide the work-up of patients with suspected PWS and to provide prognostic counseling for families.- - - - - - - - - - ranking = 0.4keywords = chromosome (Clic here for more details about this article) |
9/187. A fetus with prader-willi syndrome showing normal diurnal rhythm and abnormal ultradian rhythm on heart rate monitoring.Clinical features of prader-willi syndrome in neonates are marked hypotonia with the absence of crying and feeding difficulty so that prenatal diagnosis of prader-willi syndrome is strongly hoped in order to provide appropriate medical and psychological care for neonates and their families. However, the clinical picture of prader-willi syndrome in utero has not been well described. We report a pregnancy associated with prader-willi syndrome manifesting polyhydramnios, large biparietal diameter of the fetus and characteristic fetal heart rate pattern: prolonged inactive periods and diurnal variation of the incidence of heart rate accelerations. These findings may offer a clue to the prenatal diagnosis of prader-willi syndrome, although molecular cytogenetics is mandatory for the definite diagnosis.- - - - - - - - - - ranking = 0.0004278675867731keywords = ring (Clic here for more details about this article) |
10/187. Familial prader-willi syndrome: case report and a literature review.prader-willi syndrome (PWS) is a neurobehavioural disorder arising through a number of different genetic mechanisms. All involve loss of paternal gene expression from chromosome 15q11q13. Although the majority of cases of PWS are sporadic, precise elucidation of the causative genetic mechanism is essential for accurate genetic counselling as the recurrence risk varies according to the mechanism involved. A pair of siblings affected by PWS is described. Neither demonstrates a microscopically visible deletion in 15q11q13 or maternal disomy. Methylation studies at D15S63 and at the SNRPN locus confirm the diagnosis of PWS. Molecular studies reveal biparental inheritance in both siblings with the exception of D15S128 and D15S63 where no paternal contribution is present indicating a deletion of the imprinting centre. family studies indicate that the father of the siblings carries the deletion which, he has inherited from his mother. The recurrence risk for PWS in his offspring is 50%.- - - - - - - - - - ranking = 0.20010696689669keywords = chromosome, ring (Clic here for more details about this article) |
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