E Schwinger

Universität zu Lübeck, Lübeck Hansestadt, Schleswig-Holstein, Germany

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Publications (234)1007.63 Total impact

  • European journal of human genetics: EJHG 06/2014; · 3.56 Impact Factor
  • European journal of human genetics: EJHG 04/2014; · 3.56 Impact Factor
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    ABSTRACT: Restless legs syndrome (RLS) has a high familial aggregation. To date, several loci and genetic risk factors have been identified, but no causative gene mutation has been found. We evaluated a German family with autosomal dominantly inherited RLS in 7 definitely and 2 possibly affected members by genome-wide linkage analysis and exome sequencing. We identified three novel missense and one splice site variant in the PCDHA3, WWC2, ATRN, and FAT2 genes that segregated with RLS in the family. All four exons of the PCDHA3 gene, the most plausible candidate, were sequenced in 64 unrelated RLS cases and 250 controls. This revealed three additional rare missense variants (frequency <1%) of unknown pathogenicity in 2 patients and 1 control. We present the first next-generation sequencing study on RLS and suggest PCDHA3 as a candidate gene for RLS. © 2012 Movement Disorder Society.
    Movement Disorders 11/2012; 27(13):1686-9. · 5.63 Impact Factor
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    ABSTRACT: Männlicher Infertilität liegen in etwa einem Drittel der Fälle genetische Alterationen zugrunde. Dieser Tatsache sollte durch eine konsequente Diagnostik und umfassende Beratung des Kinderwunschpaares hinsichtlich möglicher Risiken vor Einsatz der modernen Techniken der assistierten Reproduktion Rechnung getragen werden. Major principles of genetic failures, chromosomal alterations and the most common syndroms associated with male infertility should be taken into account before medical therapy and sophisticated techniques of assisted fertilization are applied to help a couple conceive. This review addresses the most common genetic reasons of male infertility with special regard to the importance for the clinical work up in daily routine and the potential risks for conceptus.
    Der Gynäkologe 05/2012; 33(2):79-87.
  • E. Schwinger
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    ABSTRACT: Präimplantationsdiagnostik (preimplantation genetic diagnosis, PGD) wird in Deutschland zzt. nicht durchgeführt. Das Embryonenschutzgesetz verbietet nach Ansicht von Gegnern der PGD in Deutschland eine solche Diagnostik. Befürworter sind der Ansicht, dass unter bestimmter juristischer Sichtweise das Embryonenschutzgesetz einer PGD nicht entgegenstehen würde. Vor dem Hintergrund dieser Situation ist eine PGD bisher in Deutschland nicht durchgeführt worden. Die in Deutschland seit längerer Zeit heftig geführte Diskussion ist in wissenschaftlichen Kreisen des Auslandes nur schwer zu vermitteln. Preimplantation genetic diagnosis (PGD) is not presently performed in Germany. According to PGD's opponents there, existing laws for the protection of embryos forbid this type of diagnostics. Proponents feel that these laws do not stand in the way of PGD, depending on legal viewpoint. This controversy has hindered PGD's application in Germany. The nature of this longstanding, emotional discussion is not easy to describe to scientists abroad.
    Der Gynäkologe 04/2012; 33(11):795-799.
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    ABSTRACT: BACKGROUND Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are believed to destabilise genomic imprints. An increased frequency of Beckwith-Wiedemann syndrome in children born after ART has been reported. Other, mostly epidemiological, studies argue against this finding. OBJECTIVE To examine the effect of ART on the stability of DNA methylation imprints, DNA was extracted from maternal peripheral blood (MPB), umbilical cord blood (UCB) and amnion/chorion tissue (ACT) of 185 phenotypically normal children (77 ICSI, 35 IVF, and 73 spontaneous conceptions). Using bisulfite based technologies 10 differentially methylated regions (DMRs) were analysed, including KvDMR1, H19, SNRPN, MEST, GRB10, DLK1/MEG3 IG-DMR, GNAS NESP55, GNAS NESPas, GNAS XL-alpha-s and GNAS Exon1A. RESULTS Methylation indices (MI) do not reveal any significant differences at nine DMRs among the conception groups in neither MPB, UCB nor in ACT. The only slightly variable DMR was that of MEST. Here the mean MI was higher in UCB and MPB of IVF cases (mean MI+/-SD: 0.41+/-0.03 (UCB) and 0.40+/-0.03 (MPB)) compared to the ICSI (0.38+/-0.03, p=0.003 (UCB); 0.37+/-0.04, p=0.0007 (MPB)) or spontaneous cases (0.38+/-0.03, p=0.003 (UCB); 0.38+/-0.04, p=0.02 (MPB)). Weak but suggestive correlations between DMRs were, however, found between MPB, UCB and ACT. CONCLUSION This study supports the notion that children conceived by ART do not show a higher degree of imprint variability and hence do not have an a priori higher risk for imprinting disorders.
    Journal of Medical Genetics 11/2009; 47(6):371-6. · 5.70 Impact Factor
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    ABSTRACT: For prospective parents at risk of transmitting a monogenic disease, polar body analysis is an option for pre-conception genetic diagnosis. In Germany, polar body analysis is currently performed in only two centers (Lübeck and Regensburg). The authors present a clinical series of 9 couples at risk for the transmission of a monogenic disease who underwent in vitro fertilization with polar body analysis. Nine couples have undergone in vitro fertilization with polar body analysis at the center in Lübeck since 2004. Three healthy children were born after polar body analysis for mucopolysaccharidosis type I, incontinentia pigmenti, and cystic fibrosis. The decision to undergo in vitro fertilization with polar body analysis is not easy for prospective parents to take, even though it often follows years of emotional suffering. Treatment with the methods of reproductive medicine in general, and with polar body analysis in particular, can cause considerable physical and emotional stress. For prospective parents in Germany at risk of transmitting a monogenic disease, polar body-based preimplantation diagnosis is an alternative to prenatal diagnosis and possible termination of pregnancy. The live birth rate per treatment cycle in this clinical series was 30%, which can be considered satisfactory. Nonetheless, most of the couples who did not achieve pregnancy after a first treatment cycle dropped out of treatment prematurely and did not go on to a second cycle.
    Deutsches Ärzteblatt International 09/2009; 106(33):533-8. · 3.54 Impact Factor
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    ABSTRACT: Sarcoidosis is a multi-factorial systemic disease of granulomatous inflammation. Current concepts of the aetiology include interactions of unknown environmental triggers with an inherited susceptibility. Toll-like receptors (TLRs) are main components of innate immunity and therefore TLR genes are candidate susceptibility genes in sarcoidosis. Ten members of the human TLR gene family have been identified and mapped to seven chromosomal segments. The aim of this study was to investigate all known TLR gene loci for genetic linkage with sarcoidosis and to follow positive signals with different methods. We analysed linkage of TLR gene loci to sarcoidosis by use of closely flanking microsatellite markers in 83 families with 180 affected siblings. We found significant linkage between sarcoidosis and markers of the TLR4 gene locus on chromosome 9q (non-parametric linkage score 2.63, P = 0.0043). No linkage was found for the remaining TLR gene loci. We subsequently genotyped 1203 sarcoidosis patients from 997 families, 1084 relatives and 537 control subjects for four single nucleotide polymorphisms of TLR4, including Asp299Gly and Thr399Ile. This genotype data set was studied by case-control comparisons and transmission disequilibrium tests, but showed no significant results. In summary, TLR4 - w ith significant genetic linkage results - appears to be the most promising member of the TLR gene family for further investigation in sarcoidosis. However, our results do not confirm the TLR4 polymorphisms Asp299Gly and Thr399Ile as susceptibility markers. Our results rather point to another as yet unidentified variant within or close to TLR4 that might confer susceptibility to sarcoidosis.
    Clinical & Experimental Immunology 07/2008; 152(3):423-31. · 3.41 Impact Factor
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    ABSTRACT: Restless legs syndrome (RLS) is a common sensory-motor disorder characterized by paresthesias and an intense urge to move the legs with a considerable familial aggregation. To date, no gene mutation has been found, but five gene loci have been mapped in primary RLS to chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1 through 5). We identified a four-generational German RLS family with 37 family members including 15 affected cases. We performed linkage analysis using microsatellite markers at the five known loci. Prompted by the identification of a potentially shared haplotype near the RLS3 locus, we expanded the investigated linkage region on chromosome 9p using additional DNA markers. Mode of inheritance in our RLS family was compatible with an autosomal dominant pattern, and disease onset was mainly in childhood or adolescence. We excluded linkage to the RLS1, RLS2, RLS4, and RLS5 loci. However, we identified a likely new RLS gene locus (RLS3*) on chromosome 9p with a maximum lod score of 3.60 generated by model-based multipoint linkage analysis. A haplotype flanked by D9S974 and D9S1118 in a 9.9-Mb region, centromeric to RLS3, was shared by all 12 investigated patients. In addition, 11 of them carried a common haplotype extending telomeric to D9S2189 that is located within RLS3. We demonstrate linkage to a locus on chromosome 9p that is probably distinct from RLS3. Our family with a rather homogeneous phenotype and very early disease onset represents a unique opportunity to further elucidate the genetic causes of the frequent restless leg syndrome.
    Neurology 03/2008; 70(9):686-94. · 8.30 Impact Factor
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    ABSTRACT: Für Anlageträgerinnen einer monogenen Erkrankung ist die Polkörperdiagnostik (PKD) in Deutschland derzeit eine Alternative zur Pränataldiagnostik mit evtl. Schwangerschaftsabbruch. Die PKD ist praktisch die früheste Form der Präimplantationsdiagnostik (PID). Voraussetzung ist eine In-vitro-Fertilisation (IVF) mit intrazytoplasmatischer Spermieninjektion (ICSI). Ziel der PID und auch PKD für monogene Erkrankungen ist die Auswahl solcher Embryonen für den Transfer, die die in der Familie nachgewiesene entsprechende Erkrankung nicht entwickeln werden. Die PKD wurde kurz nach der PID erstmalig 1991 durch Verlinsky et al. [1] beschrieben. Aufgrund länderspezifischer gesetzlicher Regelungen sind die methodischen Möglichkeiten der Präimplantationsdiagnostik in den einzelnen Ländern heute unterschiedlich. So ist in Deutschland, Österreich, der Schweiz und seit 2004 auch in Italien [2] die Diagnostik von Embryonen mittels PID verboten.
    04/2007: pages 119-123;
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    ABSTRACT: PINK1 mutations cause recessively inherited early-onset Parkinson's disease (EOPD). We comprehensively tested 75 Serbian and 17 South Tyrolean EOPD patients for mutations in this gene and found three heterozygous mutation carriers. Two of these patients shared mutations with their affected relatives, further suggesting that heterozygous PINK1 mutations may act as a susceptibility factor for EOPD.
    Movement Disorders 10/2006; 21(9):1526-30. · 4.56 Impact Factor
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    ABSTRACT: Mutations in LRRK2 (leucine-rich repeat kinase 2) have been associated with autosomal dominant Parkinson's disease (PD) and cluster in several 3' exons of the gene. The majority of mutations have been detected in late-onset cases (age at onset >50 years). We screened 5 of the 51 exons of LRRK2 that previously have been reported to harbor mutations in 98 early-onset and 42 late-onset PD patients. We identified two mutations (c.4321C>T, c.6055G>A) in three early-onset patients. Screening of an additional 220 early-onset PD patients for these mutations revealed another mutation carrier. In conclusion, LRRK2 mutations need to be considered also in early-onset PD.
    Movement Disorders 09/2006; 21(9):1506-10. · 4.56 Impact Factor
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    ABSTRACT: Without Abstract
    Journal of Neurology 09/2006; 253(8):1111-2. · 3.58 Impact Factor
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    ABSTRACT: Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.
    Journal of Neural Transmission 08/2006; 113(7):829-43. · 3.05 Impact Factor
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    ABSTRACT: Preimplantation genetic diagnosis (PGD) may help couples at risk to avoid pregnancies with known genetic diseases. In Germany, the only option to perform PGD is the analysis of polar bodies (PB). Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder. Q70X is one of the frequent diseases causing mutations of alpha-L-iduronidase (IDUA), leading to a severe phenotype with mental retardation and various somatic abnormalities, and making a request for PGD is understandable. Using five polymorphic DNA markers from the vicinity of IDUA, PGD on first PB was performed for a consanguineous couple, both heterozygotes of the Q70X mutation of IDUA. Sixteen first PB were obtained by laser assisted hatching of the zona pellucida. Genotyping led to the conclusion that 3/16 oocytes carried wild-type IDUA alleles. Only one of these oocytes showed pronucleus formation after intracytoplasmic sperm injection and was transferred on day 2 after oocyte retrieval. A singleton pregnancy was established. Prenatal diagnosis showed a fetus heterozygous for Q70X. For MPS I, PB analysis is a feasible way to perform PGD and it may be an acceptable alternative for couples with moral objections to embryo selection, or for countries in which genetic testing of the embryo is prohibited.
    Reproductive biomedicine online 03/2006; 12(2):215-20. · 2.68 Impact Factor
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    ABSTRACT: Recent studies have suggested an association between restless legs syndrome (RLS) and Parkinson's disease (PD). We present a large multigenerational family and a smaller family with RLS. A Parkin mutation was found in 10 of 20 patients from both families with idiopathic RLS but was not considered causative. The clinical phenotype did not differ between RLS patients with and without a Parkin mutation. Inheritance of RLS was consistent with autosomal dominant transmission, and linkage analysis excluded all three known loci for RLS.
    Movement Disorders 03/2006; 21(2):258-63. · 4.56 Impact Factor
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    ABSTRACT: The spinocerebellar ataxias (SCAs) with autosomal dominant inheritance are a clinically and genetically heterogeneous group of neurodegenerative disorders. To date 24 different loci have been identified for these conditions. A locus at chromosome 16q22.1 co-segregates with the disease phenotype in families of Scandinavian, Japanese and German origin. The corresponding SCA4 locus was narrowed down to 7.94 Mb for the two European and to 1.25 Mb for Japanese pedigrees. Unfortunately, because of the phenotypic differences between patients from Japan and Europe it is not possible to decide if SCA families linked to chromosome 16q22.1 share a common disease genotype or not. To look for mutations in the German family we screened 34 candidate genes in a 3.69 cM region. With the exception of two cSNPs, no segregation of DNA variations with the disease phenotype was found.
    Journal of Neurology 01/2006; 252(12):1472-5. · 3.58 Impact Factor
  • E SCHWINGER
    Annals of Anatomy-anatomischer Anzeiger - ANN ANATOMY. 01/2006; 188(4):328-328.
  • Geburtshilfe Und Frauenheilkunde - GEBURTSH FRAUENHEILK. 01/2006; 66(9):870-875.
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    Neurology 10/2005; 65(5):761. · 8.30 Impact Factor

Publication Stats

5k Citations
1,007.63 Total Impact Points

Institutions

  • 1986–2014
    • Universität zu Lübeck
      • • Institute of Human Genetics
      • • Klinik für Frauenheilkunde und Geburtshilfe
      • • Institut für Pathologie
      • • Department of Obstetrics and Gynecology
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2004–2007
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2005
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2002
    • University of Michigan
      • Department of Ophthalmology and Visual Sciences
      Ann Arbor, MI, United States
    • Ospedale Generale Regionale "F. Miulli"
      Acquaviva delle Fonti, Apulia, Italy
  • 1983–2002
    • University of Hamburg
      • Department of Human Genetics
      Hamburg, Hamburg, Germany
  • 2000
    • University of Münster
      • Department of Psychiatry
      Münster, North Rhine-Westphalia, Germany
  • 1999
    • Christian-Albrechts-Universität zu Kiel
      Kiel, Schleswig-Holstein, Germany
  • 1998
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1989
    • University of Delhi
      • Department of Anthropology
      Delhi, NCT, India
  • 1985
    • University of Wuerzburg
      • Institute for Human Genetics
      Würzburg, Bavaria, Germany
  • 1983–1984
    • Hannover Medical School
      • Institute for Human Genetics
      Hanover, Lower Saxony, Germany