G Schwanitz

University of Bonn, Bonn, North Rhine-Westphalia, Germany

Are you G Schwanitz?

Claim your profile

Publications (173)244.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The genetic relevance of small supernumerary marker chromosomes (sSMCs) depends on their content of euchromatin. In case of mosaicism, the phenotype of the carrier furthermore is influenced by the distribution of the marker in the body. In the majority of reported cases no correlation of the degree of mosaicism in the tissue(s) analyzed and the phenotype could be detected. In particular, non-acrocentric derived sSMCs show a strong tendency to appear in mosaic state irrespective of the clinical picture. We present a patient with cognitive disability and mild craniofacial dysmorphisms with mosaicism of three different autosomal marker chromosomes. The extra chromosomes were analyzed by a combination of SNP array and a variety of fluorescence in situ hybridization (FISH) probes. All three markers were identified as ring chromosomes containing different amounts of euchromatic material derived from chromosome 1 (1p12 → q21), 12 (12p13.1 → q13.11) and 18 (18p11.21 → q11.2). The size and the frequency of the sSMCs were strikingly different, besides, we observed an unequal combination of the three derivates. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 12/2013; · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: To test the hypothesis that mutations of SYCP3 encoding synaptonemal complex protein 3, result in increased frequency of aneuploidies in humans. METHODS: Mutation analysis of the PCR-amplified 8 coding exons and exon-intron boundaries of the SYCP3 gene was done by direct sequencing of DNA isolated from 35 aneuploid fetuses of women having a potentially increased likelihood for an underlying genetic predisposition for chromosomal non-disjunction. RESULTS: Based on the results of conventional karyotyping, the 35 aneuploid fetuses of 33 women were divided into separate groups: 9 aneuploid conceptuses of couples with recurrent aneuploid conceptions (4 of the women 35 years or younger), 12 conceptuses with double/multiple aneuploidies (5 of the women 35 years or younger), and 14 conceptuses with single aneuploidies of women younger than 35 years (8 trisomies and 6 monosomies). No pathogenic mutations in the SYCP3 coding exons and the immediately flanking intronic sequences were found. CONCLUSIONS: Under the assumption that genetic predisposition for chromosomal non-disjunction leading to aneuploidy is most likely polygenic in nature, our data suggest that SYCP3 mutations are not one of the common causes in humans.
    Archives of Gynecology 05/2013; · 0.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Detailed molecular-cytogenetic studies combined with thorough clinical characterization are needed to establish genotype-phenotype correlations for specific chromosome deletion syndromes. Although many patients with subtelomeric deletions have been reported, the phenotype maps for many of the corresponding syndromes, including the terminal deletion 14q syndrome, are only slowly emerging. Here, we report on five patients with terminal partial monosomy of 14q32.3 and characteristic features of terminal deletion 14q syndrome. Four of the patients carry de novo terminal deletions of 14q, three of which have not yet been reported. One patient carries an unbalanced translocation der(14)t(9;14)(q34.3;q32.3). Minimum deletion sizes as determined by molecular karyotyping and FISH are 5.82, 5.56, 4.17, 3.54, and 3.29 Mb, respectively. Based on our findings and a comprehensive review of the literature, we refine the phenotype map for typical clinical findings of the terminal deletion 14q syndrome (i.e., intellectual disability/developmental delay, muscular hypotonia, postnatal growth retardation, microcephaly, congenital heart defects, genitourinary malformations, ocular coloboma, and several dysmorphic signs). Combining this phenotype map with benign copy-number variation data available from the Database of Genomic Variants, we propose a small region critical for certain features of the terminal deletion 14q syndrome which contains only seven RefSeq genes.
    American Journal of Medical Genetics Part A 02/2012; 158A(4):695-706. · 2.30 Impact Factor
  • Source
    Thomas Eggermann, Gesa Schwanitz
    08/2011; , ISBN: 978-953-307-631-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical follow-up over 6 years and genetic testing results of a boy with mosaic tetrasomy 14q are reported [1].The motoric and psychological development of the patient could now be followed up over a period of 7 years and showed an increasing retardation. Repeated investigations of chromosomes and interphase FISH revealed no differences in the amount of aberrant cells from peripheral blood and buccal mucosa (20-25%) during the first 2 years of life of the patient and there were no differences between buccal mucosa from right and left side. Interestingly, within the last 5 years the amount of aberrant cells almost doubled in peripheral blood (40-48%). A cultivation effect could be excluded by the analysis of native blood. Additional array investigations showed that the tetrasomic euchromatic region comprised about 14.5 Mb.
    European journal of medical genetics 03/2011; 54(4):e465-7. · 1.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two male twins born after IVF therapy were investigated for 9 years. Lymphocyte culture at the age of 1 and 9 years revealed that one twin (P1) carried a supernumerary asymmetric dic(15;15) which was present in 100% of cells. In buccal mucosa, however, the derivative 15 (der(15)) was lost in 12% of cells. The der(15) was maternal in origin and was determined to be a meiosis I abnormality. The asymmetric structure of the der(15), as demonstrated by GTG banding and microarray analysis, resulted in a tetrasomy for the region 15q11q13.2 and trisomy for 15q13.2q13.3. Both regions were interrupted by a disomic fragment of 514 kb; this region has been published as a CNV. Monosomy for this CNV was confirmed in the mother, along with a second CNV in the distal breakpoint region in 15q13.3. The patient had a second structural aberration, namely an almost complete deletion of one of the two centromeres in the der(15), such that it was not detected by metaphase or interphase FISH with the DNA probe D15Z4. The conventional karyotypes of the parents and the second twin (P2) were normal. The second twins retardation was obviously caused by an infection at the age of 4 weeks, followed by multiple organ failure. Twin P1 received special support from birth to the age of 9 years and has developed better than was to be expected from findings in the literature, while his twin brother failed to show developmental progress.
    Postzygotic Origin of Mosaicism. 01/2011;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytogenetic and molecular cytogenetic investigations from bone marrow samples were performed in 83 patients with multiple myeloma. Karyotype analyses were made after cultivation with and without growth factors. The polyploidy level ranged from 3n to 6n. For each patient the composite karyotype was delineated. The number of abnormalities per aberrant cell was in a range from 1 to 17 (x =3,7). The comparison of CGH and FISH results showed an accordance of 92%. In total, 57% of cells showed chromosomal aberrations.
    Int J Hum Genet. 01/2010; 10:217-222.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mosaic variegated aneuploidy (MVA) is characterized by multiple trisomies. The parallel existence of two non-mosaic trisomies of two different chromosomes in the fetus and the placenta has not been published to date. We report here on a putative extreme form of MVA in a pregnancy with a non-mosaic trisomy 7 in CVS and a non-mosaic trisomy 18 in amniotic fluid. The trisomy 7 was not detected in amniocytes, but a non-mosaic trisomy 18 was diagnosed. Both aneuploidies were confirmed through STR typing of the respective tissue. We infer a postzygotic mitotic origin of both aneuplodies based on the observed reduction of maternal heterozygosity to homozygosity in the analysed markers. It is indeed well conceivable that mitotic errors occur in the early embryo briefly after differentiation into trophoblast and epiblast, resulting in a complete fetal-placental discordance such as the one observed in our case. However, the observation that trisomies 7 and 18 are among the most common aberrations in MVA would support our assumption that the complete discordance of the chromosomal complement in our case represents an extreme form of MVA.
    Int J Hum Genet. 01/2009; 9:1-4.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Silver-Russell syndrome (SRS) is a heterogeneous disorder associated with intrauterine and postnatal growth retardation, skeletal asymmetry and facial dysmorphisms. In 7-10% of patients maternal uniparental disomy for chromosome 7 can be observed, nearly 50% of patients carry an epimutation resulting in hypomethylation of the imprinting center region 1 (ICR1) in 11p15. This leaves 40% of patients with unknown genetic aetiology. Based on the observation that the CTCF homologue BORIS is involved in imprinted gene expression and that it binds to methylated alleles we assumed that loss-of-function mutations in BORIS might have similar functional consequences as an ICR1 hypomethylation. On the other hand, there is evidence that BORIS mutations may disturb the methylation process and therefore cause hypomethylation in the ICR1. In our study we searched for BORIS gene mutations in a mixed cohort of SRS patients with and without 11p15 hypomethylation to determine whether this gene is involved in SRS aetiology. Mutation analyses revealed eight genomic variants but pathogenic mutations were not observed. Thus we conclude that alterations of the BORIS gene are probably not associated with SRS.
    Int J Hum Genet. 01/2009; 9:3-4.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 ± 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 ± 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 ± 1.6% for female carriers and 1.4 ± 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample. © 2008 Wiley-Liss, Inc.
    American Journal of Medical Genetics Part A 09/2008; 146A(20):2611 - 2616. · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dental malformations due to chromosomal trisomies are rarely described and need an intensive cooperation between pediatricians, orthodonticians and human geneticists to enable the collection of data and to extend the investigations on specific parameters of the teeth. Here we present tooth studies of two children with trisomies 13 (Pätau-syndrome) and 21 (Down-syndrome): the dentition, the tooth morphology and the structure as well as the composition were investigated over a period of six years. Both male patients showed a delayed and abnormal dentition. Morphologic and structural changes compared to the general population were also detectable; whereas, the composition of the teeth was unchanged in enamel, dentin, and the border between them. The abnormalities in all parameters investigated were more pronounced in the patient with Pätau-syndrome than in the child with Down-syndrome.
    Advances in Medical Sciences 08/2008; 53(1):17-20. · 0.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The female carrier of a de novo interstitial deletion 9q [karyotype 46,XX,del(9)(q31.2q33.1)] was followed up over a period of more than 20 years. She shows facial dysmorphisms and significant growth retardation. Motor abilities are restricted by muscular hypotonia and malposition of the feet. She has mental retardation. There was no speech development and phases of autism were reported. By analyses with FISH and short tandem repeat markers, the interstitial deletion was confirmed and characterized to span 9q31.2q33.1, comprising at least 7.07 Mb. The aberration is of paternal origin.
    American Journal of Medical Genetics Part A 06/2008; 146A(9):1180-4. · 2.30 Impact Factor
  • Source
    B Muss, G Schwanitz
    [Show abstract] [Hide abstract]
    ABSTRACT: KEYWORDS Pericentric inversions; paracentric inversions; comparison of euchromatic and heterochromatic rearrangements; inversion hotspots ABSTRACT Inversions comprise approximately 10% of structural aberrations, with pericentric inversions clearly outnumbering paracentric rearrangements (66% as compared to 34%), due in part to diagnostic difficulties in the latter group. At 11%, chromosome 2 displays the highest recombination frequency for euchromatic pericentric inversions, while chromosomes 3 and 7 are most often involved in paracentric inversions (16% and 19%, respectively). Inversions of the constitutive heterochromatin are far more frequent than those involving the euchromatin, totalling 20% for only 6 chromosomes. Chromosome 4 demonstrates the highest frequency of pericentric inversions (15%). The genetic risks for inversion carriers differ significantly depending on the chromosome involved and on the specific inverted region, ranging from less than 1% to a maximum of 30%. Cryptic inversions resulting in a microdeletion in chromosome 7q11.23 have been demonstrated to be causative in 33% of Williams-Beuren cases, apparently due to an abnormal course of meiosis I. Molecular cytogenetic investigations of the parents of carriers of cryptic chromosome aberrations may be expected to detect a higher frequency of paracentric inversions than has thus far been demonstrated.
    Int J Hum Genet. 01/2007; 7:141-161.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with the karyotypic finding of a terminal deletion in the long arm of chromosome 18 (18q- syndrome) commonly display cerebral dysmyelination and developmental delay. To our knowledge, all reported cases characterized by molecular analysis who had no mental retardation as confirmed by neuropsychological testing had a chromosomal breakpoint within the two most distal bands, 18q22 or 18q23, leading to a deletion of 16 Mb or less. It was the aim of this study to improve the karyotype-phenotype correlation in 18q- syndrome by thoroughly analyzing the deletion size and the mental and radiologic status in a 23-year-old woman with a terminal 18q deletion. We performed cytogenetic and molecular cytogenetic analysis, brain MRI, and extended neuropsychological testing. Molecular karyotyping revealed a 17 Mb deletion of terminal 18q with a breakpoint in 18q21.33 and no evidence for mosaicism. While brain MRI demonstrated severe global dysmyelination, the patient showed a neuropsychological pattern that allowed for normal psychosocial and job achievement. After delayed development in childhood, the patient caught up during puberty and showed normal verbal intelligence and skills at 23 years. However, visual, visual-spatial, visual-constructional, and executive functions were found to be severely impaired. Here, we present a patient with one of the largest terminal 18q deletions reported in an individual without obvious mental retardation. Our analysis extends the phenotypic spectrum for individuals with breakpoints in 18q21.33. In addition, this study highlights the fact that severe global dysmyelination may not be associated with general cognitive deficits.
    Acta Neurologica Scandinavica 09/2006; 114(2):133-8. · 2.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The study described the molecular cytogenetic characterization of myeloma cells in 130 patients via interphase fluorescence in situ hybridization. Nine repetitive DNA probes (for chromosomes 3, 7, 9, 11, 15, 17, 18, X, and Y) as well as seven single-copy DNA probes (for chromosomes 13, 17, 21, and two each for chromosomes 5 and 22) were used for the hybridizations. Using this panel of probes, we were able to show aberrations in 86% of patients. Most of them had one to three aberrations. There was a distinct correlation between the number of aberrations per patient and the tumor stage. Thus, the proportion of patients with 8-12 aberrations increased from 16% in stage II to 26% in stage III. There were marked differences among the chromosomes with respect to the prevalence of genomic losses and gains and deletions of gene loci. Chromosomes 3, 5, 7, 9, 11, 15, and 21 showed a preference for genomic gains. Losses were most often found for chromosomes 13 and 17 (locus specific) as well as for the X and Y chromosomes. The frequency of monosomies and trisomies were approximately the same for chromosomes 15 and 18, which indicates a skewed pattern of distribution. We found two specific aberrations that caused distinct changes in the survival rates of the patients: deletion 13q14 (28% of patients) and translocation of the IGH locus 14q32 (79% of 39 patients who were analyzed separately). The results obtained in this study yielded data of extremely relevant prognostic value.
    Cancer Genetics and Cytogenetics 06/2006; 167(1):20-5. · 1.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A supernumerary marker chromosome (SMC) was analysed after lymphocyte culture of a patient with oligoasthenoteratozoospermia (OAT) before ICSI treatment. By additional molecular cytogenetic investigations the marker could be identified as a heterochromatic derivate of chromosome 15 [karyotype: 47,XY,+der(15)]. Sperm analyses by interphase FISH showed a normal monosomy 15 in 82% and an additional marker in 17% of the cells. In spite of these findings a pregnancy could not be induced. The brother of the patient showed the same chromosome abnormality and an OAT-syndrome as well. ICSI-treatment lead to a normal pregnancy and to the birth of a healthy boy. The genetic risk factors of both marker carriers are analysed in detail.
    Advances in Medical Sciences 02/2006; 51:31-5. · 0.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present a 1-year-old boy with mild mental retardation, postnatal growth retardation, and facial dysmorphisms such as frontal bossing, laterally accentuated bushy eyebrows, deep set eyes with long lashes, hypertelorism, and a broad nasal bridge. Except for hip dysplasia, no congenital malformations were detected. By conventional cytogenetics a derivative chromosome 3 de novo was diagnosed which was identified as tandem dup(3)(q12q23) by fluorescence in situ hybridization (FISH) applying arm specific paints and eight different YAC-probes. The duplicated segment lies proximally from the reported dup(3q) syndrome critical region, thus explaining the absence of characteristic phenotypic features of dup(3q) syndrome. To our knowledge this is the first report of a patient with pure trisomy of this proximal region of the long arm of chromosome 3.
    European Journal of Medical Genetics 01/2006; 49(3):225-34. · 1.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chromosomal rearrangements involving the (sub)telomeres are an important cause of human genetic diseases: with the development of advanced molecular cytogenetic methods they have been identified as a major cause of mental retardation and/or congenital malformation syndromes. We identified a cryptic unbalanced de novo translocation 10p/13q by subtelomere FISH in a boy with mental and growth retardation (karyotype: 46,XY,der(10)t(10;13)(p15.1;q34)(D10S2488-,D13S296+)). Craniofacial dysmorphisms included frontal bossing, epicanthal folds, long philtrum, thin upper lip, short nose, mild retrognathy and a flat midface. In addition the patient had ASDII, a pyloric stenosis, bilateral inguinal hernias and cryptorchidism. His psychomotor development was significantly delayed. Microsatellite typing revealed the paternal origin of the two chromosomes involved in the rearrangement. By comparing our case with previously published patients with similar aberrations we conclude that the congenital malformations in our case are associated with the partial 10p deletion. The craniofacial features might be attributed to the 13q duplication. The identification of a 10p/13q translocation in our case highlights the importance of searching for cryptic subtelomeric imbalances in mentally retarded patients and helps to further delineate genotype-phenotype correlations in rare chromosomal disturbances.
    European Journal of Medical Genetics 01/2006; 49(6):505-10. · 1.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report on two cases of distal monosomy 11q and partial trisomy 16q due to a familial subtle translocation detected by FISH subtelomere screening. Exact breakpoint analyses by FISH with panels of BAC probes demonstrated a 9.3-9.5 megabase partial monosomy of 11q24.2-qter and a 4.9-5.4 megabase partial trisomy of 16q24.1-qter. The index patient displayed craniofacial dysmorphisms, mild mental retardation and postnatal growth retardation, muscular hypotonia, mild periventricular leukodystrophy, patent ductus arteriosus, thrombocytopenia, recurrent infections, inguinal hernia, cryptorchidism, pes equinovarus, and hearing deficiencies. In his mother's cousin who bears the identical unbalanced translocation, mild mental retardation, patent ductus arteriosus, hypogammaglobulinemia, recurrent infections, unilateral kidney hypoplasia, pes equinovarus, and hearing deficiencies were reported. Since only four descriptions of cryptic or subtle partial trisomies 16q have been published to date, our patients contribute greatly to the delineation of the phenotype of this genomic imbalance. In contrast to this, terminal deletions of the long arm of chromosome 11 cause a haploinsufficiency disorder (Jacobsen syndrome) in which karyotype-phenotype correlations are already being established. Here, our findings contribute to the refinement of a phenotype map for several Jacobsen syndrome features including abnormal brain imaging, renal malformations, thrombocytopenia/pancytopenia, inguinal hernia, testicular ectopy, pes equinovarus, and hearing deficiency.
    American Journal of Medical Genetics Part A 12/2005; 139(1):19-24. · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The case of monosomy 18/ring chromosome 18 mosaicism which was detected prenatally by amniocentesis is presented. The pregnancy was terminated in week 18. Autopsy showed complex malformation of the fetus consisting of cebocephaly, hypotelorism, microphthalmia, severe defects of brain development, and arrest of placental maturation.
    Prenatal Diagnosis 11/2005; 12(11):945 - 950. · 2.68 Impact Factor

Publication Stats

1k Citations
244.12 Total Impact Points

Institutions

  • 1983–2013
    • University of Bonn
      • • Institute of Human Genetics
      • • Neurologische Klinik
      Bonn, North Rhine-Westphalia, Germany
  • 1999–2009
    • RWTH Aachen University
      • Institute of Human Genetics
      Aachen, North Rhine-Westphalia, Germany
  • 2002–2008
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 2005–2006
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 1998
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
  • 1996
    • University Hospital Essen
      • Institut für Humangenetik
      Essen, North Rhine-Westphalia, Germany
  • 1969–1987
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 1975
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany