Huppke, Peter

[["dc.bibliographiccitation.firstpage","1369"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","1375"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Laccone, Franco A."],["dc.contributor.author","Kramer, N."],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T10:50:39Z"],["dc.date.available","2018-11-07T10:50:39Z"],["dc.date.issued","2000"],["dc.description.abstract","Only recently have mutations in MECP2 been found to be a cause of Rett Syndrome (RTT), a neurodevelopmental disorder characterized by mental retardation, loss of expressive speech, deceleration of head growth and loss of acquired skills that almost exclusively affects females. We analysed the MECP2 gene in 31 patients diagnosed with RTT. Sequencing of the coding region and the splice sites revealed mutations in 24 females (77.40%). However, no abnormalities were detected in any of the parents that were available for investigation. Eleven mutations have not been described previously. Confirming two earlier studies, we found that most mutations are truncating and only a few of them are missense mutations. Several females carrying the same mutation display different phenotypes indicating that factors other than the type or position of mutations influence the severity of RTT. Four females with RTT variants were included in the study. Three of these presented with preserved speech while the fourth patient with congenital RTT lacked the initial period of normal development. Detection of mutations in these cases reveals that they are indeed variants of RTT. They represent the mild and the severe extremes of RTT. Conclusions: mutations in MECP2 seem to be the main cause for RTT and can be expected to be found in similar to 77% of patients that fulfil the criteria for RTT. Therefore analysis of MECP2 should be performed if RTT is suspected. Three mutation hotspots (T158M, R168X and R255X) were confirmed and a further one (R270X) newly identified. We recommend screening for these mutations before analysing the coding region."],["dc.identifier.doi","10.1093/hmg/9.9.1369"],["dc.identifier.isi","000087354800011"],["dc.identifier.pmid","10814718"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48703"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0964-6906"],["dc.title","Rett syndrome: analysis of MECP2 and clinical characterization of 31 patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","528"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","European Journal of Pediatrics"],["dc.bibliographiccitation.lastpage","530"],["dc.bibliographiccitation.volume","161"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Wilken, Barbara"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Sattler, B."],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T09:58:54Z"],["dc.date.available","2018-11-07T09:58:54Z"],["dc.date.issued","2002"],["dc.description.abstract","We report on an 11-year-old girl who developed multiple joint contractures over a period of 3 months. The disease presented with progressive involvement of the fingers, elbows, shoulders, knees and feet and was not accompanied by other symptoms. Laboratory investigations showed eosinophilia and hypergammaglobulinaemia. Muscle ultrasound and magnetic resonance imaging of the right forearm revealed thickened fascia and a full thickness biopsy confirmed the diagnosis of eosinophilic fasciitis. Following treatment with pulsed steroids, the contractures resolved. Conclusion: our case shows that eosinophilic fasciitis can present without skin involvement and arthritis and therefore has to be regarded as a differential diagnosis of contractures in childhood. Pulsed steroid treatment was effective and without side-effects."],["dc.identifier.doi","10.1007/s00431-002-1038-1"],["dc.identifier.isi","000178831300004"],["dc.identifier.pmid","12297898"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37469"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0340-6199"],["dc.title","Eosinophilic fasciitis leading to painless contractures"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","63"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuropediatrics"],["dc.bibliographiccitation.lastpage","68"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Held, M."],["dc.contributor.author","Hanefeld, Folker"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Laccone, Franco A."],["dc.date.accessioned","2018-11-07T10:31:00Z"],["dc.date.available","2018-11-07T10:31:00Z"],["dc.date.issued","2002"],["dc.description.abstract","Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects girls. It is caused by mutations in the MECP2 gene that encodes the methyl-CpG-binding protein 2 (MeCP2). In this study we correlated mutation type and location with the severity of the phenotype in 123 girls with RTT. The ability to sit, walk, speak, hand function, head growth, occurrence of epilepsy and a combined severity score were assessed in all girls at 5 years of age and then statistically correlated with the results of the molecular genetic tests. We found that patients who carry either missense mutations or deletions located within the hotspot for deletions, an area between the base pairs (bp) 1030 and 1207 of the MECP2 gene, present with a milder phenotype than other patients. We correlated the location of the mutations with the phenotype and found that all mutations that lead to either a complete or partial truncation of the region coding for the nuclear localisation signal (NLS) are associated with a more severe phenotype than other truncating mutations (p = 0.001). We did not find a significant difference between the patients with mutations in the methyl-CpG-binding domain (MBD) and those with mutations in the transcriptional repression domain (TRD). We conclude that mutation type and location correlate with the phenotype in Rett syndrome. All mutations that impair the nuclear localisation signal (NLS) are associated with more severe phenotypes."],["dc.identifier.doi","10.1055/s-2002-32365"],["dc.identifier.isi","000176277500002"],["dc.identifier.pmid","12075485"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43997"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0174-304X"],["dc.title","Influence of mutation type and location on phenotype in 123 patients with Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","332"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Journal of Pediatrics"],["dc.bibliographiccitation.lastpage","335"],["dc.bibliographiccitation.volume","142"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Kohler, K."],["dc.contributor.author","Laccone, Franco A."],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T10:40:38Z"],["dc.date.available","2018-11-07T10:40:38Z"],["dc.date.issued","2003"],["dc.description.abstract","Objective We reevaluated 49 girls with either Rett syndrome (RTT) or features of RTT who had negative test results for mutations in the MECP2 gene and compared them with 49 girls who had positive test results. The girls with MECP2-positive results included 2 girls with forme fruste and 2 with congenital RTT. Study design Based on the original diagnostic criteria for RTT, we developed a 10-item checklist with a score ranging from 0 to 12. Results If only girls with a score of 8 or more had been tested, 46% of the girls without mutations would have been excluded from testing without missing a single girl with MECP-positive results. Conclusions This checklist provides a simple aid for deciding whether or not a genetic test for RTT should be performed with only a minimal risk of missing girls with MECP-positive results."],["dc.identifier.doi","10.1067/mpd.2003.96"],["dc.identifier.isi","000181748600025"],["dc.identifier.pmid","12640384"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46349"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mosby-elsevier"],["dc.relation.issn","1097-6833"],["dc.relation.issn","0022-3476"],["dc.title","Indication for genetic testing: A checklist for Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","21"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Dysmorphology"],["dc.bibliographiccitation.lastpage","24"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Christen, Hans-Juergen"],["dc.contributor.author","Sattler, B."],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T11:02:23Z"],["dc.date.available","2018-11-07T11:02:23Z"],["dc.date.issued","2000"],["dc.description.abstract","We report two brothers with mental retardation, lymphoedema of the limbs and facial anomalies. Hennekam et al. (Am J Med Genet 34:593-600; 1989) described four patients with identical signs and intestinal lymphangiectasia. To confirm the diagnosis of Hennekam syndrome we undertook a duodenal biopsy from the older brother which revealed intestinal lymphangiectasia. So far only one patient with Hennekam syndrome and cerebral abnormalities has been described. This patient presented with pachygyria in the parietal area. Cerebral MRI in our two cases revealed small subcortical hyperintensities in both patients and a large cystic lesion in the younger patient probably representing an old media infarction. Clin Dysmorphol 9:21-24 (C) 2000 Lippincott Williams & Wilkins."],["dc.identifier.doi","10.1097/00019605-200009010-00004"],["dc.identifier.isi","000084793300004"],["dc.identifier.pmid","10649792"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51375"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0962-8827"],["dc.title","Two brothers with Hennekam syndrome and cerebral abnormalities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1093"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","1101"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Trappe, Ralf"],["dc.contributor.author","Laccone, Franco A."],["dc.contributor.author","Cobilanschi, J."],["dc.contributor.author","Meins, M."],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Hanefeld, Folker"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T09:05:00Z"],["dc.date.available","2018-11-07T09:05:00Z"],["dc.date.issued","2001"],["dc.description.abstract","Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that apparently is lethal in male embryos. RTT almost exclusively affects female offspring and, in 99.5% of all cases, is sporadic and due to de novo mutations in the MECP2 gene. Familial cases of RTT are rare and are due to X-chromosomal inheritance from a carrier mother. We analyzed the parental origin of MECP2 mutations in sporadic cases of RTT, by analysis of linkage between the mutation in the MECP2 gene and intronic polymorphisms in 27 families with 15 different mutations, and we found a high predominance of mutations of paternal origin in 26 of 27 cases (P < .001). The paternal origin was independent of type of mutation and was found for single-base exchanges as well as for deletions. Parents were not of especially advanced age. We conclude that de novo mutations in RTT occur almost exclusively on the paternally derived X chromosome and that this is most probably the cause for the high female: male ratio observed in patients with RTT. Affected males recently have been described in a few cases of familial inheritance. Identification of the parental origin may be useful to distinguish between the sporadic form of RTT and a potentially familial form. This distinction will allow geneticists to offer more-specific counseling and discriminate between higher (maternal origin) and lower (paternal origin) recurrence risk."],["dc.identifier.doi","10.1086/320109"],["dc.identifier.isi","000168171200003"],["dc.identifier.pmid","11309679"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25226"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Univ Chicago Press"],["dc.relation.issn","0002-9297"],["dc.title","MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1257"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Acta Paediatrica"],["dc.bibliographiccitation.lastpage","1261"],["dc.bibliographiccitation.volume","90"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Roth, C."],["dc.contributor.author","Christen, Hans-Juergen"],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T11:24:51Z"],["dc.date.available","2018-11-07T11:24:51Z"],["dc.date.issued","2001"],["dc.description.abstract","Aim: To determine whether primary or secondary growth hormone (GH) deficiency has a causative role in linear growth retardation, a key feature in Rett syndrome (RTT). Methods: In 38 patients with Rett syndrome a variable set of investigations was performed including assays of growth and thyroid hormones, gonadotropins, gonadal and adrenal steroids and determination of bone age. Not all measurements were attainable from all patients. In three patients the 24-h growth hormone secretion profile was evaluated using the pulsar method. Results: The bone age determined in 24 patients was found to be normal in 8, retarded in 9 and accelerated in 7 patients. Insulin-like growth factor (IGF)-1 was low in 8 out of 23 patients. IGF-binding protein (IGFBP)-3 and insulin and arginine-stimulatcd growth hormone secretion were both nornial, indicating normal GH secretion in the majority of patients. The 24-h CH secretion profile in the first patient showed a normal day/night rhythm and a normal increase in nocturnal GH secretion. The second patient's overall GH secretion was normal but there was no day/night rhythm. The third patient showed borderline low GH secretion. Normal age-appropriate plasma values were found for the thyroid hormones (T4, TSH), TSH-night rhythm, oestradiol, prolactin and cortisol (08.00, 18.00). Conclusion: Our study provides no evidence that growth retardation in RTT is caused by growth hormone deficiency. A disturbed hypothalamic control cannot be excluded but it is unlikely that this is the major cause of growth retardation in RTT."],["dc.identifier.isi","000172785300010"],["dc.identifier.pmid","11808895"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56501"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis As"],["dc.relation.issn","0803-5253"],["dc.title","Endocrinological study on growth retardation in Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","941"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Epilepsia"],["dc.bibliographiccitation.lastpage","945"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","von Moers, A."],["dc.contributor.author","Brockmann, Knut"],["dc.contributor.author","Wang, D."],["dc.contributor.author","Korenke, C. G."],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","De Vivo, D. C."],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T10:12:47Z"],["dc.date.available","2018-11-07T10:12:47Z"],["dc.date.issued","2002"],["dc.description.abstract","Purpose: Glut-1 deficiency syndrome (Glut-1 DS) is caused by the deficiency of the major glucose transporter in cerebral microvessels. Methods: We performed pre- and postprandial EEG recordings in two unrelated children with Glut-1 DS with developmental delay and seizures predominantly in the morning before breakfast. Results: Extensive epileptiform discharges observed in the fasting state were improved markedly by food intake, as documented in EEG recordings 1 and 2 h after a meal. The ratio of cerebrospinal fluid glucose to blood glucose was decreased in both children. Glut-1 deficiency was confirmed by biochemical and molecular genetic investigations. Conclusions: Pre- and postprandial EEG recordings offer a simple screening test for Glut-1 DS."],["dc.identifier.doi","10.1046/j.1528-1157.2002.50401.x"],["dc.identifier.isi","000177383900024"],["dc.identifier.pmid","12181017"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40304"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing Inc"],["dc.relation.issn","0013-9580"],["dc.title","EEG features of Glut-1 deficiency syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","105"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neuropediatrics"],["dc.bibliographiccitation.lastpage","108"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Bohlander, S. K."],["dc.contributor.author","Kramer, N."],["dc.contributor.author","Laccone, Franco A."],["dc.contributor.author","Hanefeld, Folker"],["dc.date.accessioned","2018-11-07T10:31:01Z"],["dc.date.available","2018-11-07T10:31:01Z"],["dc.date.issued","2002"],["dc.description.abstract","Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects girls. Recently mutations in MECP2, that encodes the methyl CpG binding protein 2 (MeCP2), have been found to cause RTT. MeCP2 has a role in gene silencing. It binds to methylated cytosine in the DNA and recruits histone deacetylases. We studied the methylation pattern of the promoters of two X chromosomal genes, G6PD and SYBL1, in patients with RTT and in a control group. Both genes undergo X inactivation which correlates with promoter methylation. A 1 : 1 ratio of methylated versus non-methylated alleles was expected. In the control group a median ratio of 47:53 of methylated to non-methylated alleles was found at the GGPD promoter locus. In 22 patients with RT7 the median ratio was significantly different, 33:67 (p < 0.0001). Analysis of the SYBL1 promoter revealed an almost identical median ratio of methylated versus non-methylated alleles (RTT 47: 53; control 49: 51), however, the range was wider in the RTT group (RTT 23:77 to 56:44; control 43: 57 to 55:45). There was no apparent correlation between G6PD promoter methylation status and mutations in the MeCP2 gene or the severity of the clinical phenotype in our patient group. The finding of reduced methylation at the G6 PD promoter is an interesting finding and suggests that there could be widespread dysregulation of X chromosomal genes in Rett syndrome."],["dc.identifier.doi","10.1055/s-2002-32373"],["dc.identifier.isi","000176277500011"],["dc.identifier.pmid","12075494"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43998"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0174-304X"],["dc.title","Altered methylation pattern of the G6 PD promoter in Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","346"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Brain and Development"],["dc.bibliographiccitation.lastpage","351"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Held, Melanie"],["dc.contributor.author","Hanefeld, Folker"],["dc.contributor.author","Laccone, Franco A."],["dc.date.accessioned","2021-06-01T10:50:17Z"],["dc.date.available","2021-06-01T10:50:17Z"],["dc.date.issued","2003"],["dc.description.abstract","Since the discovery of mutations in the methyl-CpG binding protein-2 (MECP2) gene in Rett Syndrome (RTT) a large number of females have been diagnosed worldwide. In this article we present the clinical and developmental data of 120 RTT females with mutations in the MECP2 gene and individually describe typical and atypical cases. We found a broad spectrum of phenotypes in females. At the severest end we have females with primary developmental delay who never learned to turn, sit or walk and who developed severe epilepsy. At the mildest end of the spectrum, there are females with only minor neurological symptoms who have good gross motor function, speak and have relatively well-preserved hand function. A number of girls either do not fulfil all the necessary diagnostic criteria or present with symptom.,; that have not been described in RTT before. Comparing our data with the normal population we found that girls with RTT have a smaller occipito-frontal circumference, shorter length and lower weight at birth. As a result of molecular genetic analysis a broad spectrum of phenotypes in RTT females has evolved. We found evidence that the defect in MeCP2 influences the somatic growth before birth. (C) 2003 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0387-7604(03)00018-4"],["dc.identifier.isi","000184309900009"],["dc.identifier.pmid","12850514"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86598"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0387-7604"],["dc.title","The spectrum of phenotypes in females with Rett Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]