35 results on '"Klaus Zerres"'
Search Results
2. Cortico-limbic connectivity in MAOA -L carriers is vulnerable to acute tryptophan depletion
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Florian D. Zepf, Mikhail Zvyagintsev, Klaus Zerres, Dhana Wolf, Klaus Mathiak, Thomas Eggermann, Krystyna A. Mathiak, Patrick Eisner, Pegah Sarkheil, Albrecht Eisert, and Martin Klasen
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Serotonergic ,Amygdala ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,Prefrontal cortex ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Resting state fMRI ,biology ,030227 psychiatry ,medicine.anatomical_structure ,nervous system ,Neurology ,biology.protein ,Neurology (clinical) ,Serotonin ,Anatomy ,Monoamine oxidase A ,Functional magnetic resonance imaging ,Psychology ,Insula ,Neuroscience ,psychological phenomena and processes ,030217 neurology & neurosurgery - Abstract
INTRODUCTION A gene-environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene-environment interaction. METHODS Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. RESULTS Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. CONCLUSION MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene-environment interaction. Hum Brain Mapp 38:1622-1635, 2017. © 2016 Wiley Periodicals, Inc.
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- 2016
3. Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype ofBICD2mutations
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Thomas Eggermann, Florian Deden, Alfred Yamoah, Anand Goswami, Bernd Sellhaus, Kristl G. Claeys, Katja Eggermann, Dagmar Wieczorek, Joachim Weis, Klaus Zerres, and Sabine Rudnik-Schöneborn
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0301 basic medicine ,Weakness ,Physiology ,Upper motor neuron ,Spinal muscular atrophy ,Anatomy ,Gene mutation ,Biology ,medicine.disease ,Lower motor neuron ,Muscle atrophy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Physiology (medical) ,Corticospinal tract ,medicine ,Spinal muscular atrophy with lower extremity predominance ,Neurology (clinical) ,medicine.symptom ,030217 neurology & neurosurgery - Abstract
Introduction Heterozygous BICD2 gene mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED). Methods We analyzed the BICD2 gene in a selected group of 25 index patients with neurogenic muscle atrophy. Results We identified 2 new BICD2 missense mutations, c.2515G>A, p.Gly839Arg, in a family with autosomal dominant inheritance, and c.2202G>T, p.Lys734Asn, as a de novo mutation in an isolated patient with similar phenotype. The patients had congenital foot contractures, muscle atrophy of the legs, and slowly progressive weakness of the shoulder girdle. There was no apparent sensory or brain dysfunction. One patient died of unrelated reasons at age 52 years. Autopsy revealed no upper motor neuron and only moderate lower motor neuron loss, but there was distal corticospinal tract degeneration and marked neurogenic muscular atrophy. Conclusion These findings give further insight into the clinical and pathoanatomical consequences of BICD2 mutations. Muscle Nerve 54: 496–500, 2016
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- 2016
4. NSD1duplication in Silver-Russell syndrome (SRS): molecular karyotyping in patients with SRS features
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Katja Eggermann, Klaus Zerres, Miriam Elbracht, Alexia Bach, Andrea Luczay, Nadina Ortiz Brüchle, Jana Sachwitz, György Fekete, Vaidutis Kučinskas, Thomas Eggermann, Stephanie Spranger, Aušra Matulevičienė, and Robert Meyer
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0301 basic medicine ,Genetics ,Chromosome 7 (human) ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Sotos syndrome ,Silver–Russell syndrome ,Karyotype ,Biology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,parasitic diseases ,Gene duplication ,Cohort ,medicine ,Copy-number variation ,Genetics (clinical) ,Genetic testing - Abstract
Silver-Russell syndrome (SRS) is a growth retardation syndrome characterized by intrauterine and postnatal growth retardation, relative macrocephaly and protruding forehead, body asymmetry and feeding difficulties. Nearly 50% of cases show a hypomethylation in 11p15.5, in 10% maternal uniparental disomy of chromosome 7 is present. A significant number of patients with SRS features also exhibit chromosomal aberrations. We analyzed 43 individuals referred for SRS genetic testing by molecular karyotyping. Pathogenic variants could be detected in five of them, including a NSD1 duplication in 5q35 and a 14q32 microdeletion. NSD1 deletions are detectable in overgrowth disorders (Sotos syndrome and Beckwith-Wiedemann syndrome), whereas NSD1 duplications are associated with growth retardation. The 14q32 deletion is typically associated with Temple syndrome (TS14), but the identification of a patient in our cohort reflects the clinical overlap between TS14 and SRS. As determination of molecular subtypes is the basis for a directed counseling and therapy, the identification of pathogenic variants in >10% of the total cohort of patients referred for SRS testing and in >16% of characteristic individuals with the characteristic SRS phenotype confirms the need to apply molecular karyotyping in this cohort.
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- 2016
5. Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a German genetic laboratory on the basis of 1206 index patients
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Uwe Kornak, Janbernd Kirschner, Katja Eggermann, K von Au, Jan Senderek, Wolfgang Müller-Felber, M. von der Hagen, C. Bußmann, D. Tölle, Dagmar Wieczorek, Barbara Leube, Ulrike Schara, Miriam Elbracht, Klaus Zerres, and Sabine Rudnik-Schöneborn
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0301 basic medicine ,Genetics ,Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Genetic data ,Diagnostic algorithms ,Biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Gene duplication ,Mutation (genetic algorithm) ,medicine ,Mutation detection ,Clinical severity ,Genetic diagnosis ,030217 neurology & neurosurgery ,Genetics (clinical) ,Genetic testing - Abstract
We present clinical features and genetic results of 1206 index patients and 124 affected relatives who were referred for genetic testing of Charcot-Marie-Tooth (CMT) neuropathy at the laboratory in Aachen between 2001 and 2012. Genetic detection rates were 56% in demyelinating CMT (71% of autosomal dominant (AD) CMT1/CMTX), and 17% in axonal CMT (24% of AD CMT2/CMTX). Three genetic defects (PMP22 duplication/deletion, GJB1/Cx32 or MPZ/P0 mutation) were responsible for 89.3% of demyelinating CMT index patients in whom a genetic diagnosis was achieved, and the diagnostic yield of the three main genetic defects in axonal CMT (GJB1/Cx32, MFN2, MPZ/P0 mutations) was 84.2%. De novo mutations were detected in 1.3% of PMP22 duplication, 25% of MPZ/P0, and none in GJB1/Cx32. Motor nerve conduction velocity was uniformly 40 m/s in MFN2, and more variable in GJB1/Cx32, MPZ/P0 mutations. Patients with CMT2A showed a broad clinical severity regardless of the type or position of the MFN2 mutation. Out of 75 patients, 8 patients (11%) with PMP22 deletions were categorized as CMT1 or CMT2. Diagnostic algorithms are still useful for cost-efficient mutation detection and for the interpretation of large-scale genetic data made available by next generation sequencing strategies.
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- 2015
6. Pontocerebellar hypoplasia
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Klaus Zerres, Peter G. Barth, and Sabine Rudnik-Schöneborn
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Pediatrics ,medicine.medical_specialty ,business.industry ,Genetics ,Pontocerebellar hypoplasia ,Medicine ,Medical genetics ,business ,medicine.disease ,Genetics (clinical) - Published
- 2014
7. Brugada-like cardiac disease in myotonic dystrophy type 2: report of two unrelated patients
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Sabine Rudnik-Schöneborn, Wolfram Kress, A. Lindner, Klaus Zerres, S. Zumhagen, Miriam Elbracht, M. Schaupp, and E. Schulze-Bahr
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musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Genetic heterogeneity ,Cardiomyopathy ,Disease ,medicine.disease ,Sudden cardiac death ,Proximal myotonic myopathy ,Neurology ,Cardiac Conduction Disorder ,Internal medicine ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,Neurology (clinical) ,Family history ,business ,Brugada syndrome - Abstract
Background: Myotonic dystrophy type 2 (DM2) is an autosomal dominant multisystem disorder caused by CCTG repeat expansions within intron 1 of the ZNF9 gene on chromosome 3q. Cardiac conduction disturbances, supraventricular arrhythmias, and cardiomyopathy are described in DM2 but Brugada-like features have not yet been reported. Brugada syndrome (BS) is a genetically heterogeneous cardiac conduction disorder which is characterized by a significant ST-segment elevation upon ECG evaluations and bears an increased risk for sudden cardiac death. Case reports: We report two unrelated patients with genetically confirmed DM2 who developed clinical relevant cardiac arrhythmias with syncopal events from 35 (patient 1) and 47 years (patient 2). Brugada-like ECG findings were present in both patients. Family history was negative for BS, but the mothers of both index patients were also affected by DM2 and had different ventricular rhythm disturbances. SCN5A gene sequencing revealed an unknown genetic variant c.4140 C > A, p.N1380K, in patient 1, while no mutation was detected in patient 2. Discussion: Our observations may suggest that Brugada-like cardiac arrhythmias can occur in DM2, as this seems also to be the case in DM1. The chance association of two independent inherited disorders has to be considered and cannot be excluded in one of our patients. However, on statistical grounds, this possibility cannot explain all observed cases of DM with Brugada-like cardiac disease.
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- 2010
8. Megalencephaly, mega corpus callosum, and complete lack of motor development: Delineation of a rare syndrome
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Martin Häusler, Meike Hengst, Jens Tücke, Klaus Zerres, and Marcus Blaum
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Muscular hypotonia ,business.industry ,Developmental Disabilities ,Hypertrophy ,Anatomy ,medicine.disease ,Corpus callosum ,Magnetic Resonance Imaging ,Corpus Callosum ,Motor Skills Disorders ,Central nervous system disease ,Rare Diseases ,Atrophy ,Neuroimaging ,Child, Preschool ,Genetics ,medicine ,Polymicrogyria ,Humans ,Female ,Megalencephaly ,Agenesis of Corpus Callosum ,business ,Genetics (clinical) ,Motor skill - Abstract
Unlike atrophy of the corpus callosum (CC), callosal hypertrophy is a rare neuroimaging finding with only few reported patients. The "megalencephaly, mega CC, and complete lack of motor development" syndrome is morphologically characterized by generalized megalencephaly, a thickened CC, and extensive polymicrogyria causing a pachygyric appearance. We report on the fifth patient showing this rare syndrome, a 3-year-old girl displaying the typical neuroimaging features. Clinically she showed a severely impaired motor, mental, and speech development with marked muscular hypotonia but no dysmorphic facial signs. She also retained the ability to move by rolling sidewards so that complete lack of motor development may not be a consistent feature.
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- 2010
9. Digital necroses and vascular thrombosis in severe spinal muscular atrophy
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Silke Vogelgesang, Luitgard Graul-Neumann, Klaus Zerres, Sven Armbrust, Sabine Rudnik-Schöneborn, and Christoph Fusch
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Male ,Pathology ,medicine.medical_specialty ,Physiology ,Gene Dosage ,Sural nerve ,SMN1 ,Spinal Muscular Atrophies of Childhood ,Fingers ,Central nervous system disease ,Necrosis ,Cellular and Molecular Neuroscience ,Fatal Outcome ,Physiology (medical) ,Skin Ulcer ,Biopsy ,medicine ,Humans ,Venous Thrombosis ,medicine.diagnostic_test ,business.industry ,Vascular disease ,Heart Septal Defects ,Infant, Newborn ,Infant ,Spinal muscular atrophy ,Motor neuron ,medicine.disease ,SMA ,Magnetic Resonance Imaging ,nervous system diseases ,Survival of Motor Neuron 2 Protein ,medicine.anatomical_structure ,nervous system ,Female ,Neurology (clinical) ,business - Abstract
Infantile spinal muscular atrophy (SMA) caused by homozygous SMN1 gene deletions/mutations is characterized by neuronal loss and axonopathy of motor neurons. We report two unrelated patients with severe SMA type I who had only one SMN2 copy and developed ulcerations and necroses of the fingers and toes. Sural nerve biopsy was normal in patient 1, whose affected skin displayed necroses and thrombotic occlusions of small vessels. Corresponding to a mouse model and other patients with similar findings, we believe that severe survival motor neuron (SMN) deficiency may present as vasculopathy.
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- 2010
10. Genetic variation in the schizophrenia-risk gene neuregulin 1 correlates with brain activation and impaired speech production in a verbal fluency task in healthy individuals
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Sören Krach, Thomas Eggermann, Nadim Joni Shah, Tilo Kircher, Klaus Zerres, Tony Stöcker, Tim Becker, Carin Whitney, Axel Krug, Valentin Markov, Markus M. Nöthen, Marcella Rietschel, and Jens Treutlein
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Adult ,Male ,Psychosis ,Neuregulin-1 ,Neuropsychological Tests ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Brain mapping ,Speech Disorders ,Young Adult ,Speech Production Measurement ,Functional neuroimaging ,mental disorders ,Image Processing, Computer-Assisted ,medicine ,Humans ,Verbal fluency test ,Radiology, Nuclear Medicine and imaging ,Research Articles ,Brain Mapping ,Neural correlates of consciousness ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,Verbal Behavior ,Brain ,Cognition ,medicine.disease ,Magnetic Resonance Imaging ,Semantics ,Oxygen ,Neurology ,Schizophrenia ,Female ,Neurology (clinical) ,Anatomy ,Functional magnetic resonance imaging ,Psychology ,Cognitive psychology - Abstract
Impaired performance in verbal fluency tasks is an often replicated finding in schizophrenia. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and temporal areas. Since schizophrenia has a high heritability, it is of interest whether susceptibility genes for the disorder, such as NRG1, modulate verbal fluency performance and its neural correlates. Four hundred twenty‐nine healthy individuals performed a semantic and a lexical verbal fluency task. A subsample of 85 subjects performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (MRI). NRG1 (SNP8NRG221533; rs35753505) status was determined and correlated with verbal fluency performance and brain activation. For the behavioral measure, there was a linear effect of NRG1 status on semantic but not on lexical verbal fluency. Performance decreased with number of risk‐alleles. In the fMRI experiment, decreased activation in the left inferior frontal and the right middle temporal gyri as well as the anterior cingulate gyrus was correlated with the number of risk‐alleles in the semantic verbal fluency task. NRG1 genotype does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in schizophrenia and may explain some of the cognitive and brain activation variation found in the disorder. More generally, NRG1 might be one of several genes that influence semantic language capacities. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
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- 2009
11. Genetic counseling in Robertsonian translocations der(13;14): Frequencies of reproductive outcomes and infertility in 101 pedigrees
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Thomas Eggermann, Barbara Panasiuk, Klaus Zerres, Anna Jelska, Hartmut Engels, Anna Latos-Bielenska, Alina T. Midro, Lucjusz Jakubowski, Jacek Zaremba, Herdit M. Schüler, Gesa Schwanitz, Almut Caliebe, and Regine Schubert
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Infertility ,medicine.medical_specialty ,Genetic counseling ,Robertsonian translocation ,Genetic Counseling ,Prenatal diagnosis ,Fertilization in Vitro ,Biology ,medicine.disease_cause ,Translocation, Genetic ,Miscarriage ,Pregnancy ,Genetics ,medicine ,Humans ,Genetics (clinical) ,Chromosomes, Human, Pair 14 ,Chromosomes, Human, Pair 13 ,Obstetrics ,Pregnancy Outcome ,Stillbirth ,medicine.disease ,Pedigree ,Abortion, Spontaneous ,Karyotyping ,Female ,Live birth ,Trisomy - 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.
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- 2008
12. Childhood manifestation of autosomal dominant polycystic kidney disease: no evidence for genetic heterogeneity
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H Kääriäinen, D. E. Müller-Wiefel, Paul Landais, Gerard Lucotte, Andreas Gal, Klaus Zerres, Brunhilde Wirth, and Gabriele Gillessen-Kaesbach
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Genetic Markers ,Male ,Genetic Linkage ,030232 urology & nephrology ,Autosomal dominant polycystic kidney disease ,Chromosome Disorders ,Locus (genetics) ,Disease ,Biology ,urologic and male genital diseases ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Genetic linkage ,Prenatal Diagnosis ,Genetics ,Polycystic kidney disease ,medicine ,Humans ,Child ,Genetics (clinical) ,Genes, Dominant ,030304 developmental biology ,Chromosome Aberrations ,Cystic kidney ,Polycystic Kidney Diseases ,0303 health sciences ,urogenital system ,Genetic heterogeneity ,Genetic Carrier Screening ,Infant, Newborn ,Chromosome Mapping ,medicine.disease ,female genital diseases and pregnancy complications ,Pedigree ,Genetic marker ,Child, Preschool ,Female ,DNA Probes - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) usually becomes symptomatic between the third and fifth decades. We studied ten families segregating for ADPKD in which children were observed with typical manifestations of the disease at birth or in early childhood. In these families, linkage analysis was carried out with a cloned DNA sequence from the alpha-globin locus known to be closely linked to the disease gene in adult onset ADPKD. In the families studied here, close linkage (theta max = 0.09 at zmax = 2.32) was also observed between the marker and disease loci. These results provide no evidence for genetic heterogeneity of ADPKD in families with early and adult onset.
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- 2008
13. The Johanson-Blizzard syndrome: report of a new case with special reference to the dentition and review of the literature
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E. A. Holtgrave and Klaus Zerres
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medicine.medical_specialty ,Pediatrics ,Microcephaly ,Ectodermal dysplasia ,Hearing loss ,Dwarfism ,Nose ,Ectodermal Dysplasia ,Internal medicine ,Genetics ,medicine ,Humans ,Child ,Genetics (clinical) ,Autosomal recessive inheritance ,Psychomotor retardation ,Dentition ,Tooth Abnormalities ,business.industry ,Syndrome ,medicine.disease ,Johanson–Blizzard syndrome ,Endocrinology ,Female ,medicine.symptom ,business - Abstract
We report a new case of Johanson-Blizzard syndrome. The clinical findings with special reference to the dentition are discussed, and the literature is reviewed. The reported case underlines the heterogeneity of ectodermal dysplasias mentioned by Freire-Maia (1971).
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- 2008
14. Successful transplantation in a child with rapid progression of autosomal recessive polycystic kidney disease associated with a novel mutation
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Martina, Prelog, Carsten, Bergmann, Michael J, Ausserlechner, Helmut, Fischer, Raimund, Margreiter, Ingmar, Gassner, Andrea, Brunner, Therese C, Jungraithmayr, Klaus, Zerres, Consolato, Sergi, E Consolato, Sergi, and Lothar Bernd, Zimmerhackl
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medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,DNA Mutational Analysis ,Mutation, Missense ,Receptors, Cell Surface ,Kidney ,Nephrectomy ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Dialysis ,Kidney transplantation ,Polycystic Kidney, Autosomal Recessive ,Transplantation ,business.industry ,Homozygote ,Kidney metabolism ,Autosomal recessive polycystic kidney disease (ARPKD) ,medicine.disease ,Kidney Transplantation ,Autosomal Recessive Polycystic Kidney Disease ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Disease Progression ,Female ,business ,Kidney disease - Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is the most common pediatric renal cystic disease with liver involvement. The vast majority of patients with ARPKD carry mutations in the recently characterized PKHD1 gene on chromosome 6p12. A Turkish female demonstrated rapid growth of both kidneys after delivery. Accelerated growth of both kidneys and increasing respiratory distress necessitated right-sided nephrectomy at the age of three months. Because of persistent dyspnea and ongoing growth of the remaining kidney, the second kidney also had to be removed one month later. Biopsies taken from the kidney and the liver confirmed the diagnosis of ARPKD histologically. Renal ultrasound of the patient's consanguineous parents and her older brother showed normal results. PKHD1 mutation analysis yielded a novel homozygous missense mutation (c.1116C >G, F372L) in exon 14, coding for an Ig-like domain (TIG), possibly involved in the increased growth of the kidneys. Peritoneal dialysis was performed for 12 months. The patient had successful transplantation at the age of 15 months and is doing well with actual immunosuppression with cyclosporine, mycophenolate mofetil, and prednisolone. In conclusion, the present case clearly demonstrates the favorable outcome of a child with severe ARPKD after bilateral nephrectomy, pre-emptive dialysis, and successful transplantation.
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- 2006
15. Hsp27-2D-gel electrophoresis is a diagnostic tool to differentiate primary desminopathies from myofibrillar myopathies
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Dirk Fischer, Matthias Vorgerd, Lev G. Goldfarb, Kanefusa Kato, Bertrand Goudeau, Udo Roth, Rolf Schröder, Anna Kamińska, Thomas Eggermann, Klaus Zerres, Stéphanie Simon, Patrick Vicart, Angelika A. Noegel, Christoph S. Clemen, Bruno Eymard, and Norma B. Romero
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Molecular Sequence Data ,HSP27 Heat-Shock Proteins ,2D-gel electrophoresis ,Biophysics ,Biology ,Biochemistry ,Desmin ,Diagnosis, Differential ,Myofibrillar myopathies ,Hsp27 ,Structural Biology ,Heat shock protein ,Genetics ,medicine ,Humans ,Protein Isoforms ,Electrophoresis, Gel, Two-Dimensional ,Amino Acid Sequence ,Phosphorylation ,Muscle, Skeletal ,MALDI ,Molecular Biology ,Heat-Shock Proteins ,Two-dimensional gel electrophoresis ,alpha-Crystallin B Chain ,Skeletal muscle ,Cell Biology ,Plectin ,Hydrogen-Ion Concentration ,Molecular biology ,αB-crystallin ,Neoplasm Proteins ,Blot ,medicine.anatomical_structure ,biology.protein ,sense organs ,hsp27 ,Myofibril ,Molecular Chaperones ,Myopathies, Structural, Congenital - Abstract
Small heat shock proteins prevent abnormal protein folding and accumulation. We analyzed the expression of hsp27 and alphaB-crystallin in skeletal muscle specimens of patients with desminopathies, plectinopathies, myotilinopathy, and other myofibrillar myopathies by means of differential centrifugation, 2D-gel electrophoresis, Western blotting, and mass spectrometry. Hsp27-P82 and -P15 as well as alphaB-crystallin-P59 and -P45 are the major serine phosphorylation isoforms in normal and diseased human skeletal muscle. 2D-gel-electrophoresis revealed spots of hsp27 in a range of pH 5.3-6.4 in samples of all skeletal muscle specimens, except for the seven desminopathies. They indicated a shift of the main hsp27-spot to alkaline pH degrees, which may help to differentiate primary desminopathies from other myopathies with structural pathology of the desmin cytoskeleton.
- Published
- 2005
16. Premature ovarian failure associated with a small terminal Xq deletion: narrowing the POF1 region down to Xq27.2/Xq27.3-qter
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Thomas Eggermann, D Gläser, S Palm, Bernhard Horsthemke, Klaus Zerres, Katja Eggermann, F Haverkamp, Herdit M. Schüler, and D Meschede
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Genetics ,Text mining ,Terminal (electronics) ,business.industry ,Genetic counseling ,medicine ,Karyotype ,Biology ,medicine.disease ,business ,Genetics (clinical) ,Premature ovarian failure - Published
- 2005
17. New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene
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Thomas Eggermann, Helena Kääriäinen, Jan Senderek, Sabine Rudnik-Schöneborn, Markus Moser, Reinhard Buettner, Klaus Zerres, Jürgen Kunze, T Mononen, Carsten Bergmann, and Jutta Kirfel
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Genetics ,business.industry ,Haplotype ,Prenatal diagnosis ,Consanguinity ,Disease ,Bioinformatics ,medicine.disease ,Autosomal Recessive Polycystic Kidney Disease ,Genetic linkage ,Mutation (genetic algorithm) ,Medicine ,business ,Genetics (clinical) ,Kidney disease - Abstract
Due to the poor prognosis of severe autosomal recessive polycystic kidney disease (ARPKD), there is a strong demand for prenatal diagnosis (PD). Reliable PD testing is possible by molecular genetic analysis only. Although haplotype-based analysis is feasible in most cases, it is associated with a risk of misdiagnosis in families without pathoanatomically proven diagnosis. Linkage analysis is impossible in families where DNA of the index patient is not available. Direct mutation analysis of the recently identified polycystic kidney and hepatic disease 1 gene opens new options in families to whom a reliable PD cannot be offered on the basis of linkage analysis. We for the first time report two cases with PD based on mutation detection, illustrating the new options for PD in ARPKD.
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- 2004
18. Clinical and genetic heterogeneity in Desbuquois dysplasia
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Arnold Munnich, Valérie Cormier-Daire, Pierre Maroteaux, Laurence Faivre, Deborah Scheffer, Mongi Ben Hariz, Klaus Zerres, Ian D. Young, and Martine Le Merrer
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Genetic Markers ,Joint Instability ,Male ,Adolescent ,Locus (genetics) ,Biology ,Ossification center ,Osteochondrodysplasias ,Short stature ,Genetic Heterogeneity ,Gene mapping ,medicine ,Humans ,Abnormalities, Multiple ,Inbreeding ,Femur ,Child ,Genetics (clinical) ,Genetics ,Genetic heterogeneity ,Infant, Newborn ,Chromosome Mapping ,Anatomy ,Hand Deformities ,Disease gene identification ,medicine.disease ,Body Height ,Pedigree ,Tarsal Bone ,medicine.anatomical_structure ,Dysplasia ,Face ,Female ,medicine.symptom ,Chromosomes, Human, Pair 17 ,Microsatellite Repeats - Abstract
Desbuquois dysplasia is a rare chondrodysplasia of autosomal recessive inheritance characterized by short stature, joint laxity, facial anomalies, a "Swedish key" appearance of the proximal femur, and advanced carpal and tarsal bone age. Patients with Desbuquois dysplasia can be divided in two groups, depending on whether hand changes include an extra ossification center distal to the second metacarpal and whether phalangeal dislocations are present or absent. We have recently reported linkage of a Desbuquois dysplasia gene to 17q25.3 in a group of patients with typical hand abnormalities. Here, we report on the exclusion of the 17q25.3 locus in three inbred Desbuquois families originated from Turkey, Asia, and Morocco without typical hand abnormalities. Microsatellite DNA markers from the 17q25.3 region were used at an average spacing of 2 cM, and the three affected individuals from families 1 to 3 were heterozygous for the 17q25.3 region. These results allow us to exclude this region as the locus in Desbuquois families with no hand anomalies and demonstrate genetic heterogeneity. Ongoing studies will hopefully lead to the identification of the responsible genes.
- Published
- 2004
19. Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)
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Christoph Hübner, Robert A. Ouvrier, Haluk Topaloglu, Heidemarie Neitzel, Nathalie Goemans, Christina Steglich, Carmen Navarro, Piroschka Stolz, Francesco Muntoni, Friedrich Bosch, Enrico Bertini, Kate Bushby, Ulf-Peter Guenther, Hanns Lochmüller, Katja Grohmann, Stephan Eichholz, Padraic Grattan-Smith, Sabine Rudnik-Schöneborn, Markus Schuelke, Raymonda Varon, Coleen Adams, Lionel Van Maldergem, Tilman Polster, Catrin Janetzki, and Klaus Zerres
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Pediatrics ,medicine.medical_specialty ,Pathology ,Respiratory distress ,business.industry ,Respiratory disease ,Muscle weakness ,Prenatal diagnosis ,Spinal muscular atrophy ,Sudden infant death syndrome ,medicine.disease ,Central nervous system disease ,Degenerative disease ,Neurology ,medicine ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) is the second anterior horn cell disease in infants in which the genetic defect has been defined. SMARD1 results from mutations in the gene encoding the immunoglobulin mu-binding protein 2 (IGHMBP2) on chromosome 11q13. Our aim was to review the clinical features of 29 infants affected with SMARD1 and report on 26 novel IGHMBP2 mutations. Intrauterine growth retardation, weak cry, and foot deformities were the earliest symptoms of SMARD1. Most patients presented at the age of 1 to 6 months with respiratory distress due to diaphragmatic paralysis and progressive muscle weakness with predominantly distal lower limb muscle involvement. Sensory and autonomic nerves are also affected. Because of the poor prognosis, there is a demand for prenatal diagnosis, and clear diagnostic criteria for infantile SMARD1 are needed. The diagnosis of SMARD1 should be considered in infants with non-5q spinal muscular atrophy, neuropathy, and muscle weakness and/or respiratory distress of unclear cause. Furthermore, consanguineous parents of a child with sudden infant death syndrome should be examined for IGHMBP2 mutations.
- Published
- 2003
20. Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients
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Rainer Hoffmann, Peter Hanrath, A. Von Korff, Klaus Zerres, and Jan R. Ortlepp
- Subjects
medicine.medical_specialty ,education.field_of_study ,business.industry ,Clinical Biochemistry ,Population ,General Medicine ,medicine.disease ,Biochemistry ,Gastroenterology ,Calcitriol receptor ,Genotype frequency ,Coronary artery disease ,Coronary arteries ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,medicine ,Vitamin D and neurology ,Risk factor ,education ,business ,Allele frequency - Abstract
Background Recent studies found a relationship between Vitamin D and atherosclerosis. A common genetic polymorphism of the Vitamin D receptor (VDR) has been associated with coronary artery disease (CAD) in small study populations. To assess its influence on the prevalence and severity of CAD we studied a large-scale population. Methods A total of 3441 consecutive patients were referred for diagnostic coronary angiography. The BsmI Vitamin D receptor polymorphism was analyzed by polymerase chain reaction. Angiography was used to define phenotypes with clear coronary arteries (n = 775), coronary sclerosis (diameter stenosis 50% in at least one vessel; n = 1524). Patients with CAD at a young age (females aged less than 65 years, males aged less than 55 years; n = 563) were specially defined as premature CAD. The risk profile of traditional cardiovascular risk factors was obtained for every patient. Results The genotype frequencies of the VDR BsmI polymorphism did not differ between all four phenotypes (P = 0·756). The allele frequencies for the B allele were 0·43 vs. 0·44 vs. 0·42 vs. 0·45 in the four phenotypic groups (P = 0·827). All traditional cardiovascular risk factors (hypercholesterolaemia, smoking, hypertension, diabetes mellitus, severe obesity, male gender) were significantly (P
- Published
- 2003
21. Consequences of a novel caveolin-3 mutation in a large German family
- Author
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Ingmar Blümcke, Horst Urbach, Dirk Fischer, Rolf Schröder, Anja Schroers, Wilhelm Mortier, Klaus Zerres, and Matthias Vorgerd
- Subjects
Genetics ,Mutation ,Pathology ,medicine.medical_specialty ,Nonsense mutation ,Muscle weakness ,Biology ,medicine.disease ,medicine.disease_cause ,Caveolin 3 ,Atrophy ,Neurology ,cardiovascular system ,medicine ,Missense mutation ,Neurology (clinical) ,medicine.symptom ,Myopathy ,Limb-girdle muscular dystrophy - Abstract
Mutations in the human caveolin-3 gene (cav-3) on chromosome 3p25 have been described in limb girdle muscular dystrophy, rippling muscle disease, hyperCKemia, and distal myopathy. Here, we describe the genetic, myopathological, and clinical findings in a large German family harboring a novel heterozygous mutation (GACGAA) in codon 27 of the cav-3 gene. This missense mutation causes an amino acid change from asparagine to glutamate (Asp27Glu) in the N-terminal region of the Cav-3 protein, which leads to a drastic decrease of Cav-3 protein expression in skeletal muscle tissue. In keeping with an autosomal dominant mode of inheritance, this novel cav-3 mutation was found to cosegregate with neuromuscular involvement in the reported family. Ultrastructural analysis of Cav-3–deficient muscle showed an abnormal folding of the plasma membrane as well as multiple vesicular structures in the subsarcolemmal region. Neurological examination of all nine subjects from three generations harboring the novel cav-3 mutation showed clear evidence of rippling muscle disease. However, only two of these nine patients showed isolated signs of rippling muscle disease without muscle weakness or atrophy, whereas five had additional signs of a distal myopathy and two fulfilled the diagnostic criteria of a coexisting limb girdle muscular dystrophy. These findings indicate that mutations in the human cav-3 gene can lead to different and overlapping clinical phenotypes even within the same family. Different clinical phenotypes in caveolinopathies may be attributed to so far unidentified modifying factors/genes in the individual genetic background of affected patients. Ann Neurol 2003
- Published
- 2003
22. Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy
- Author
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Liv Marie Lægreid, Michael Huppke, Jürgen Seeger, Klaus Zerres, Sabine Rudnik-Schöneborn, Gunnar Houge, László Sztriha, Brunhilde Wirth, and Gururaj R. Aithala
- Subjects
Pathology ,medicine.medical_specialty ,Muscle biopsy ,medicine.diagnostic_test ,business.industry ,Pontocerebellar hypoplasia ,Muscle weakness ,Spinal muscular atrophy ,Consanguinity ,medicine.disease ,Hypotonia ,Olivopontocerebellar atrophy ,Atrophy ,Genetics ,Medicine ,medicine.symptom ,business ,Genetics (clinical) - Abstract
Pontocerebellar hypoplasia (PCH) is rarely associated with anterior horn cell disease and designated as PCH-1. This phenotype is characterized by severe muscle weakness and hypotonia starting prenatally or at birth with a life span not exceeding a few months in most cases. Milder disease courses with later onset and longer survival are normally not diagnosed as PCH-1. We describe the clinical and neuroradiological findings in nine patients out of six siblingships with evidence of cerebellar defects and early onset spinal muscular atrophy (SMA), representing a broad spectrum of clinical variability. In all patients, the diagnosis of SMA (Werdnig-Hoffmann disease) was made on the basis of electrophysiological data and muscle biopsy; however, genetic testing failed to confirm the diagnosis of infantile SMA with a gene defect on chromosome 5q and resulted in clinical reevaluation. Age at onset was after a normal period in the first months of life in three siblingships and pre- and postnatally in the other three families. Life span was 2–4 years in patients with later onset, and age at death occurred after birth or within months in the more severe group. Two siblingships showed discordant ages at death despite similar treatment. In contrast to the previous definition of PCH-1, our observations suggest the existence of milder phenotypes with pontocerebellar hypoplasia or olivopontocerebellar atrophy in combination with anterior horn cell loss. A pontine involvement is not necessarily seen by neuroimaging methods. The genetic basis of PCH-1 remains to be determined. The gene locus for infantile SMA on chromosome 5q could be excluded by linkage studies. Parental consanguinity and affected siblings make autosomal recessive inheritance most likely. © 2002 Wiley-Liss, Inc.
- Published
- 2002
23. Refinement of the autosomal recessive polycystic kidney disease (PKHD1) interval and exclusion of an EF hand-containing gene as aPKHD1 candidate gene
- Author
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Thomas Eggermann, Lisa M. Guay-Woodford, Yasuyuki Nagasawa, Luiz F. Onuchic, Carsten Bergmann, Ellis D. Avner, Xiaoying Hou, Laszlo Furu, Gregory G. Germino, Stefan Somlo, Klaus Zerres, and Michal Mrug
- Subjects
Male ,Candidate gene ,Positional cloning ,Molecular Sequence Data ,Gene Expression ,Receptors, Cell Surface ,Locus (genetics) ,Biology ,Gene mapping ,Polycystic kidney disease ,medicine ,Humans ,Genetic Predisposition to Disease ,Amino Acid Sequence ,RNA, Messenger ,Genetics (clinical) ,Polycystic Kidney, Autosomal Recessive ,Genetics ,Base Sequence ,Contig ,Chromosome Mapping ,Blotting, Northern ,medicine.disease ,Autosomal Recessive Polycystic Kidney Disease ,Genetic marker ,Chromosomes, Human, Pair 6 ,Female ,Microsatellite Repeats - Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is an often devastating form of polycystic kidney disease that presents primarily in infancy. The locus, PKHD1 (polycystic kidney and hepatic disease 1), on chromosome 6p21.1-p12, has been linked to all classical forms of this disorder. In previous studies, we cloned the PKHD1 interval in a set of overlapping YACs, converted this YAC-based framework into a BAC/PAC contig, and delimited the critical interval to a region flanked by the markers D6S1714 and D6S1024. We now have refined the genetic interval using new polymorphic markers developed from our BAC/PAC resources. In addition, we have evaluated a recently identified, EF hand-containing gene that maps to the interval of interest, established its transcript sequence, defined its genomic organization, and excluded this new gene as a PKHD1 candidate. Therefore, this study has narrowed the PKHD1 interval and excluded a potentially relevant gene as a PKHD1 candidate gene. This further refinement of the PKHD1 interval will facilitate efforts to identify the PKHD1 gene by positional cloning. These data also provide additional, highly polymorphic markers for haplotype-based diagnostic testing for ARPKD.
- Published
- 2002
24. Enuresis and urinary incontinence in children and adolescents with spinal muscular atrophy
- Author
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Sabine Rudnik-Schöneborn, M. Backes, C. Laufersweiler-Plass, A von Gontard, and Klaus Zerres
- Subjects
medicine.medical_specialty ,Stress incontinence ,Pediatrics ,business.industry ,Urology ,Urinary system ,Urinary incontinence ,CBCL ,Spinal muscular atrophy ,SMA ,medicine.disease ,Atrophy ,Enuresis ,medicine ,Physical therapy ,medicine.symptom ,business - Abstract
Objective To assess the rate and type of urinary incontinence in a large sample of children and adolescents with spinal muscular atrophy (SMA), a genetic disorder characterized by loss of motor function caused by anterior horn degeneration. Patients, subjects and methods The study included 96 severely incapacitated patients with SMA (aged 6.0–18.11 years) who were examined in detail, including a structured interview (Kinder-DIPS), the Child Behaviour Checklist (CBCL) and a specific questionnaire for urinary incontinence. They were compared with two control groups of unaffected siblings and normal children. Results In all, 29% of the patients were wet at night and/or during the day; mostly younger children with SMA types I and II only were affected. The results of the interview were more reliable than the CBCL. The specific questionnaire revealed a variety of possible functional and neurogenic forms of wetting, including nocturnal enuresis, voiding postponement, dysfunctional voiding, stress, symptomatic (urinary tract infections, UTIs) and neurogenic incontinence. Many patients were constipated, soiled or had UTIs. The rate of behavioural problems was twice as high (32%) as normal (15%; CBCL). Conclusion Children with SMA have a high rate of urinary incontinence which is often overlooked, and not diagnosed and treated adequately. These problems should be addressed routinely by paediatricians in children referred to paediatric urological specialists.
- Published
- 2001
25. Adult syndrome allelic to limb mammary syndrome (LMS)?
- Author
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Thomas F. Wienker, Klaus Zerres, Peter Propping, Waltraut Friedl, and Siegfried Uhlhaas
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ectrodactyly ,Genotype ,Genetic Linkage ,Limb Deformities, Congenital ,Limb–mammary syndrome ,Internal medicine ,medicine ,Humans ,Abnormalities, Multiple ,Breast ,Syndactyly ,Child ,Alleles ,Genetics (clinical) ,business.industry ,Syndrome ,Anatomy ,Aplasia ,medicine.disease ,Hypoplasia ,Pedigree ,Hypodontia ,Endocrinology ,Dysplasia ,Chromosomal region ,Female ,Chromosomes, Human, Pair 3 ,business - Abstract
In 1993, we described an autosomal-dominant syndrome in a German family characterized by ectrodactyly/syndactyly, dysplasia of nails, lacrimal duct atresia, hypodontia, hypoplastic breasts and nipples, intensive freckling (ADULT syndrome, acro-dermato-ungual-lacrimal-tooth syndrome, MIM 103285). In 1996 a large Dutch family with an autosomal-dominant syndrome ("limb mammary syndrome", LMS, MIM *603543) characterized by hypoplasia/aplasia of mammary glands and nipples, ectrodactyly, other hand/foot anomalies, lacrimal-duct atresia, nail dysplasia, hypohidrosis, cleft palate/bifid uvula, hypodontia was reported. In this family the disease locus was recently mapped to the chromosomal region 3q27 through a genome-wide linkage screen. Given the similarity of manifestations we hypothesized that the two syndromes might be allelic. We genotyped 21 members of the ADULT family with 19 polymorphic markers from the chromosomal region 3q27 and obtained a maximal lod score of 4.82 at straight theta = 0.00 with marker D3S1288. Our results place the ADULT locus to the same chromosomal region where LMS was mapped, suggesting that these two conditions are allelic.
- Published
- 2000
26. Syndrome of autosomal recessive polycystic kidneys with skeletal and facial anomalies is not linked to the ARPKD gene locus on chromosome 6p
- Author
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R. Schumacher, Klaus Zerres, Sabine Rudnik-Schöneborn, H. Müntefering, P. Shahidi‐Asl, Gabi Mücher, B. Wellek, Nicolai Kohlschmidt, Christian Hallermann, Franz Bahlmann, and U. Theile
- Subjects
medicine.medical_specialty ,Pathology ,Genetic heterogeneity ,Biology ,Cystic Change ,medicine.disease ,Autosomal Recessive Polycystic Kidney Disease ,Endocrinology ,Genetic linkage ,Internal medicine ,medicine ,Cyst ,Hypertelorism ,medicine.symptom ,Genetics (clinical) ,Potter Syndrome ,Kidney disease - Abstract
We report on two sibs, both males, one born at 37 the other at 24 weeks of gestation, both with a syndrome similar to that seen in three sets of sibs by Gillessen-Kaesbach et al. [1993: Am J Med Genet 45:511–518]. Both propositi had polycystic kidneys and hepatic fibrosis indistinguishable from that seen in autosomal recessive polycystic kidney disease (ARPKD), and skeletal and facial anomalies. Skeletal abnormalities included “butterfly” vertebrae, square shape of pelvis, and brachymelia. The facial anomalies included hypertelorism, epicanthic folds, and anteverted nares. Additional external findings were apparently low-set ears and a short neck. Histopathological examination of the kidneys showed radial orientation and cystic dilatation of the cortical and medullar tubules. The liver showed “congenital hepatic fibrosis.” The hepatic findings in the second infant were less severe. Renal abnormalities were limited to focal tubular cystic changes. Linkage analysis with polymorphic markers of the region 6p21.1-p12, flanking the gene locus of ARPKD, showed different haplotypes in the sibs, thus excluding the ARPKD gene locus in this family and indicating genetic heterogeneity. Am. J. Med. Genet. 90:115–119, 2000 © 2000 Wiley-Liss, Inc.
- Published
- 2000
27. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): Molecular genetics, clinical experience, and fetal morphology
- Author
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G. Mucher, Stefan Somlo, J. Becker, G.G. Germino, John M. Stockwin, L.A. Harman, C. Steinkamm, Lisa M. Guay-Woodford, P. Heikkil, R. Salonen, Ellis D. Avner, Luiz F. Onuchic, J. Rapola, S. Rudnik-Schnewborn, and Klaus Zerres
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Urology ,030232 urology & nephrology ,Morphology (biology) ,Prenatal diagnosis ,urologic and male genital diseases ,Ultrasonography, Prenatal ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Molecular genetics ,Prenatal Diagnosis ,Internal medicine ,medicine ,Humans ,Cyst ,Genetics (clinical) ,Polycystic Kidney, Autosomal Recessive ,Fetus ,business.industry ,Obstetrics ,Infant, Newborn ,Infant ,Gestational age ,Autosomal recessive polycystic kidney disease (ARPKD) ,medicine.disease ,Autosomal Recessive Polycystic Kidney Disease ,Chromosome Banding ,Pedigree ,3. Good health ,Endocrinology ,Haplotypes ,030220 oncology & carcinogenesis ,Child, Preschool ,Female ,business ,Kidney disease - Abstract
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common hereditary renal cystic diseases and has a high infant mortality. Prenatal diagnosis using fetal sonography can be unreliable, especially in early pregnancy. The ARPKD locus has been mapped to proximal chromosome 6p allowing haplotype-based prenatal diagnosis in "at-risk" families. From December 1994 to March 1997, we received 258 inquiries regarding prenatal evaluation and we have completed analyses in 212 families. To date, 65 prenatal analyses have been performed in 57 families. In the majority of the requesting families (45/57), the index children are deceased and their DNA was extracted from paraffin-embedded tissue. Eighteen fetuses were homozygous for the disease-associated haplotypes. In 12 of these fetuses, pathoanatomical examination demonstrated typical ARPKD changes consisting of dilated collecting ducts and the characteristic hepatic ductal plate malformation. These changes were detected in two fetuses as early as 13 weeks gestational age. These cases represent the earliest demonstration of ARPKD-associated histopathology reported to date. One high risk fetus was carried to term and turned out to be unaffected. However, the diagnosis of ARPKD remained doubtful in the index patient. Forty-three fetuses were either heterozygous or homozygous for a nondisease-associated haplotype and all infants born were phenotypically unaffected at birth. In four cases, a recombination event occurred between the flanking markers and no genotypic prediction was possible. Three of these pregnancies were terminated and necropsy of the fetuses confirmed ARPKD, while one fetus was carried to term and showed no abnormalities at birth. These results show that haplotype-based prenatal testing is feasible and reliable in pregnancies "at risk" for ARPKD. An absolute prerequisite for these studies is an accurate diagnosis of ARPKD in previously affected sib(s).
- Published
- 1998
28. Congenital axonal neuropathy caused by deletions in the spinal muscular atrophy region
- Author
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Brunhilde Wirth, Klaus Zerres, Guido Stoll, Sabine Rudnik-Schöneborn, A. Baborie, Benedikt Volk, U.-P. Ketelsen, M. Graf, M. Sauer, Rudolf Korinthenberg, and Clemens Oliver Hanemann
- Subjects
Denervation ,Asphyxia ,business.industry ,External ophthalmoplegia ,Anatomy ,Spinal muscular atrophy ,Motor neuron ,medicine.disease ,Central nervous system disease ,medicine.anatomical_structure ,Degenerative disease ,nervous system ,Neurology ,medicine ,Neurology (clinical) ,Brainstem ,medicine.symptom ,business - Abstract
Three newborn siblings presented with generalized weakness, asphyxia, facial diplegia, and external ophthalmoplegia. Electrophysiological testing showed inexcitability of motor and sensory nerves and myographic signs of denervation. Nerve biopsies and postmortem examination showed loss of myelinated fibers and axonal damage in sensory and mixed nerves. Many spinal motor neurons were chromatolytic although their number was normal. Molecular genetic investigations revealed a homozygous deletion of the survival motor neuron (SMN) gene and a loss of markers Ag1-CA and C212 in the paternal haplotype. These findings are consistent with the diagnosis of an unusually severe type of spinal muscular atrophy. Given the large extent of the deletion, it must be considered that the unusual severe phenotype with involvement of brainstem nuclei and afferent nerves might also be due to changes of yet unknown genes neighboring the SMN gene.
- Published
- 1997
29. Rare proximal interstitial deletion of chromosome 4q, del(4)(q13.2q21.22): New case and comparison with the literature
- Author
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Inge Heil, Thomas Eggermann, Klaus Zerres, Katja Eggermann, Herdit M. Schüler, and Carsten Bergmann
- Subjects
Genetics ,Chromosome ,Karyotype ,Biology ,Genetics (clinical) - Published
- 2005
30. Autosomal recessive polycystic kidney disease in 115 children: clinical presentation, course and influence of gender
- Author
-
F Deget, Karl Schärer, U Holtkamp, J. Geisert, Klaus Zerres, Sabine Rudnik-Schöneborn, and J. Brodehl
- Subjects
medicine.medical_specialty ,Pediatrics ,Kidney ,business.industry ,Urinary system ,Renal function ,General Medicine ,Autosomal recessive polycystic kidney disease (ARPKD) ,medicine.disease ,Autosomal Recessive Polycystic Kidney Disease ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Polycystic kidney disease ,business ,Survival rate ,Kidney disease - Abstract
The clinical course of 66 boys and 49 girls with autosomal recessive polycystic kidney disease recruited from departments of paediatric nephrology was investigated over a mean observation period of 4.92 years. This is a selected study group of children from departments of paediatric nephrology who in most cases survived the neonatal period, since birth clinics did not participate. The median age at diagnosis was 29 days (prenatal to 14.5 years). We observed decreased glomerular filtration rates (GFRs) in 72% (median age at onset of decrease of GFR < 2 SD, 0.6 years; range, 0-18.7 years), and 11 patients developed end-stage renal disease. Hypertension requiring drug treatment was found in 70% (median age at start of medication, 0.5 years; range, 0-16.7 years). Kidney length was above the 97th centile in 68% of patients, and kidney length did not increase with age or deterioration of renal function. Urinary tract infections occurred in 30%, growth retardation in 25%, and clinical signs of hepatic fibrosis were detected in 46%. Thirteen patients (11%) died during the observation period, 10 of them in the first year of life. There was a statistically significant sex difference in terms of a more pronounced progression in girls. The survival probability at 1 year was 94% for male patients and 82% for female patients (p < 0.05) in this study. Urinary tract infections occurred more frequently in girls (p < 0.025) and were observed earlier. In addition, more girls had impaired renal function, developed end-stage renal disease and showed growth retardation; these differences, however, were not significant. For the children in this study, however, our results indicate that the long-term prognosis in the majority of cases is better throughout childhood and youth than often stated.
- Published
- 1996
31. Prenatal prediction in families with autosomal recessive proximal spinal muscular atrophy (5q11.2–q13.3): Molecular genetics and clinical experience in 109 cases
- Author
-
E. Hahnen, Brunhilde Wirth, Sabine Rudnik-Schöneborn, Dorothee Röhrig, and Klaus Zerres
- Subjects
Genetic Markers ,Pediatrics ,medicine.medical_specialty ,Pathology ,Genotype ,Genetic Linkage ,Molecular Sequence Data ,Chorionic villus sampling ,Polymerase Chain Reaction ,Muscular Atrophy, Spinal ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Diagnostic Errors ,Alleles ,Genetics (clinical) ,Proximal spinal muscular atrophy ,Fetus ,Base Sequence ,medicine.diagnostic_test ,business.industry ,Haplotype ,Obstetrics and Gynecology ,Spinal muscular atrophy ,medicine.disease ,SMA ,Chromosomes, Human, Pair 5 ,Female ,business - Abstract
Prenatal prediction in families at risk for autosomal recessive proximal spinal muscular atrophy (SMA) mainly of type I is often requested due to the high incidence and the fatal outcome of the disease. So far, only indirect genotype analysis can be performed in SMA families, since the gene has not yet been identified. We present our experience of 109 prenatal diagnoses obtained in 91 families by use of single- and multi-locus polymorphic microsatellites of the region 5q11.2–q13.3. The marker combinations and specific features of the closest microsatellites are described in detail. From 137 requests for prenatal prediction of SMA between October 1991 and August 1994, 28 families were excluded, mostly because the clinical diagnosis was uncertain or doubtful. Others had to be classified as ‘SMA-variants’ or showed autosomal dominant transmission of SMA. Of the 109 prenatal diagnoses performed, 29 fetuses were diagnosed to be at high risk (>99 per cent) of developing the disease, while in seven additional pregnancies no exact prediction could be made due to a recombination event in one parental haplotype. Altogether, recombinations between closely flanking markers were observed in 14 cases. In 35 cases, the parents decided to terminate the pregnancy. Of the remaining pregnancies, 32 could be followed beyond term. All infants were reported to develop normally without signs of SMA. Two children were born with transverse reduction defects of one hand, which was most likely related to early chorionic villus sampling at 9 and 10 weeks' gestation. No further abnormalities could be detected. The limits of indirect genotype analysis and the problems of diagnostic accuracy and heterogeneity of proximal SMA are discussed.
- Published
- 1995
32. ADULT-syndrome: An autosomal-dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia, and hypodontia
- Author
-
Peter Propping and Klaus Zerres
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ectodermal dysplasia ,Ectrodactyly ,Eye disease ,Nails, Malformed ,Fingers ,Variable Expression ,Tooth Loss ,Ectodermal Dysplasia ,Lacrimal Duct Obstruction ,Internal medicine ,medicine ,Humans ,Abnormalities, Multiple ,Child ,Genetics (clinical) ,Anodontia ,Genes, Dominant ,Permanent teeth ,business.industry ,fungi ,Syndrome ,Middle Aged ,Toes ,medicine.disease ,Dermatology ,Pedigree ,stomatognathic diseases ,Hypodontia ,Endocrinology ,Nail disease ,Child, Preschool ,Agenesis ,Female ,business ,Pigmentation Disorders - Abstract
We describe a family with at least seven living persons who are affected by an hitherto undescribed autosomal-dominant syndrome with variable expression, bearing close resemblance to the EEC syndrome and related disorders. The main manifestations are hypodontia and/or early loss of permanent teeth, ectrodactyly, obstruction of lacrimal ducts, onychodysplasia, and excessive freckling. We propose the acronym ADULT (acro-der-mato-ungual-lacrimal-tooth)-syndrome for this condition. © 1993 Wiley-Liss, Inc.
- Published
- 1993
33. Isolated cystinuria (OMIM 238200) is not a separate entity but is caused by a mutation in the cystinuria gene SLC7A9
- Author
-
Thomas Eggermann, C Schmidt, F Haverkamp, Klaus Zerres, and Miriam Elbracht
- Subjects
Male ,DNA Mutational Analysis ,Cystine ,Biology ,Diagnosis, Differential ,chemistry.chemical_compound ,Genetics ,medicine ,Humans ,Polyendocrinopathies, Autoimmune ,Transcription factor ,Gene ,Genetics (clinical) ,Isolated cystinuria ,Cystinuria ,medicine.disease ,Pedigree ,chemistry ,Mutation ,Mutation (genetic algorithm) ,Amino Acid Transport Systems, Basic ,Female ,Differential diagnosis ,Transcription Factors - Published
- 2007
34. Mosaicism of isochromosome 18p
- Author
-
Klaus Zerres, I. Muradow, Manfred Hansmann, and H. Göcke
- Subjects
Fetus ,Pathology ,medicine.medical_specialty ,Philtrum ,medicine.diagnostic_test ,Isochromosome ,Obstetrics and Gynecology ,Prenatal diagnosis ,Occiput ,Anatomy ,Biology ,medicine.disease ,medicine.anatomical_structure ,Tetrasomy 18p ,Retrognathia ,embryonic structures ,medicine ,Amniocentesis ,Genetics (clinical) - Abstract
The first case of isochromosome 18p as a mosaic in a male fetus diagnosed by amniocentesis is reported. After termination of the pregnancy at 21 weeks gestation biopsies from different fetal organs as well as from the placenta were taken and set up for long term cell cultures. The distribution of the normal and abnormal cell-line in fetal organs was unequal. Unexpectedly the metaphases in the placenta and the lymphocyte culture all showed a normal karyotype. The tetrasomy 18p is associated with a uniform phenotype, even in fetal life, characterized by a small head with protuberant occiput, low-set ears with posterior rotation, epicanthic fold, sharp pinched nose, convex and poorly formed philtrum, high-arched palate, retrognathia, flexion contractures of fingers, short and broad hallux, hypoplastic penis, angulation of clavicles and mild scoliosis. The propositus showed no growth retardation.
- Published
- 1986
35. Three sibs with achalasia and alacrimia: A separate entity different from triple-A syndrome
- Author
-
Klaus Zerres, F. Haverkamp, and R. Rosskamp
- Subjects
Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Eye disease ,Achalasia ,Consanguinity ,Triple-A syndrome ,Sister ,digestive system ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Humans ,Esophagus ,Child ,Glucocorticoids ,Genetics (clinical) ,business.industry ,Syndrome ,medicine.disease ,digestive system diseases ,Esophageal Achalasia ,Normal adrenal function ,medicine.anatomical_structure ,Endocrinology ,Child, Preschool ,Female ,business ,Separate legal entity - Abstract
We report on two brothers and one sister with achalasia and alacrimia born to consanguineous unaffected parents. The combination of achalasia and alacrimia may represent an entity different from the triple-A syndrome in showing normal adrenal function.
- Published
- 1989
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