Anne-Karoline Ebert

Universität Ulm, Ulm, Baden-Württemberg, Germany

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Publications (15)37.9 Total impact

  • Anne-Karoline Ebert, Wolfgang Rösch
    Nature Reviews Urology 10/2013; · 4.79 Impact Factor
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    ABSTRACT: We report 4 patients with upper urinary tract (UUT) obstruction requiring ureteric reimplantation at 1, 7, 28, and 63 months after dextranomer/hyaluronic acid copolymer (Dx/HA) injection for vesicoureteric reflux. Histopathologic evaluation of ureteric segments revealed extensive foreign body formation in all cases. We conclude that UUT obstruction is a rare but serious complication after Dx/HA injection that can occur even years after surgery. The incidence of delayed-onset UUT obstruction may be higher than previously noted. Long-term follow-up and a critical reappraisal of the method are needed to assess the late sequelae of Dx/HA injection therapy for vesicoureteric reflux.
    Urology 03/2013; 81(3):659-62. · 2.42 Impact Factor
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    ABSTRACT: BACKGROUND: The exstrophy-epispadias complex (BEEC) is a urogenital birth defect of varying severity. The causes of the BEEC are likely to be heterogeneous, with individual environmental or genetic risk factors still being largely unknown. In this study, we aimed to identify de novo causative copy number variations (CNVs) that contribute to the BEEC. METHODS Array-based molecular karyotyping was performed to screen 110 individuals with BEEC. Promising CNVs were tested for de novo occurrence by investigating parental DNAs. Genes located in regions of rearrangements were prioritized through expression analysis in mice to be sequenced in the complete cohort, to identify high-penetrance mutations involving small sequence changes. RESULTS A de novo 0.9 Mb microduplication involving chromosomal region 19p13.12 was identified in a single patient. This region harbors 20 validated RefSeq genes, and in situ hybridization data showed specific expression of the Wiz gene in regions surrounding the cloaca and the rectum between GD 9.5 and 13.5. Sanger sequencing of the complete cohort did not reveal any pathogenic alterations affecting the coding region of WIZ. CONCLUSIONS The present study suggests chromosomal region 19p13.12 as possibly involved in the development of CBE, but further studies are needed to prove a causal relation. The spatiotemporal expression patterns determined for the genes encompassed suggest a role for Wiz in the development of the phenotype. Our mutation screening, however, could not confirm that WIZ mutations are a frequent cause of CBE, although rare mutations might be detectable in larger patient samples. 19p13.12, microduplication, bladder exstrophy-epispadias complex, array-based molecular karyotyping, in situ hybridization analysis, copy number variations, WIZ Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 01/2013; · 2.27 Impact Factor
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    ABSTRACT: PURPOSE: To assess the risk for the exstrophy-epispadias-complex (EEC) following treatment for infertility with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), two assisted reproductive techniques (ART). MATERIALS AND METHODS: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (OR) (95% confidence intervals [CI]) were determined to quantify associations using logistic regression. RESULTS: In total, 123 EEC patients born between 1997 and 2011 in Germany, who were recruited through participating departments of paediatric urology and paediatric surgery throughout Germany and the German self-help organisations Blasenekstrophie/Epispadie e.V. and Kloakenekstrophie, were included. Controls were all German live-births (n=10,069,986) born between 1997 and 2010. Overall, 12 cases (10%) and 129,982 controls (1%) were born after treatment with IVF or ICSI. Conception by ART was associated with an over eight times higher risk of EEC compared to spontaneous conception (OR, 8.3; 95% CI, 4.6-15.0; P<0.001). Separate analyses showed a significantly increased risk for EEC after treatment with IVF (OR, 14.0; 95% CI, 6.5-30.0; P<0.0001) as well as after treatment with ICSI (OR, 5.3; 95% CI, 2.2-12.9; P<0.0001). CONCLUSIONS: The present study provides evidence that assisted reproductive techniques such as IVF and ICSI go along with a strongly increased risk of having a child with EEC. However, it remains unclear whether our finding may be due to ART per se and/or due to underlying infertility/subfertility aetiology or characteristics of the parents.
    The Journal of urology 11/2012; · 3.75 Impact Factor
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    ABSTRACT: PURPOSE: To investigate bladder biopsies from patients with classical bladder exstrophy (BE) for their histological features and discuss the potential clinical significance of the findings. DESIGN AND METHODS: From 2004 to 2011 bladder tissues were collected from patients with BE. These were obtained at the time of primary bladder closure (group I, n=29), during secondary reconstructive procedures (group II, n=27) or during cystectomy for failed reconstruction (group III, n=15). All tissues specimens were investigated for inflammatory, proliferative, meta- and dysplastic changes. Expression of urothelial differentiation markers CK13 and CK20 was determined by immunohistochemistry. RESULTS: Inflammatory, proliferative and metaplastic changes were found in bladder specimens of all subgroups. Neither dysplasia nor neoplasia was present. Severe epithelial changes such as cystitis glandularis and intestinal metaplasia were observed in up to 62% of bladders several years after primary closure. Aberrant expression patterns of CK13 and CK20 suggesting abnormal urothelial differentiation were shown to be present in the urothelium of all subgroups. CONCLUSION: Our findings provide prima facie evidence that the epithelial changes observed in the unclosed bladder template persist or even progress in a subset of bladders after primary closure. Although the malignant potential of cystitis glandularis and intestinal metaplasia is controversial, some bladders may be at increased risk of developing dys-/neoplasia in the long term. As the natural history of these lesions in the exstrophic bladder is unknown, patients require lifelong surveillance.
    The Journal of urology 09/2012; · 3.75 Impact Factor
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    ABSTRACT: Epispadias is the mildest phenotype of the human bladder exstrophy-epispadias complex (BEEC), and presents with varying degrees of severity. This urogenital birth defect results from a disturbance in the septation process, during which separate urogenital and anorectal components are formed through division of the cloaca. This process is reported to be influenced by androgen signaling. The human PARM1 gene encodes the prostate androgen-regulated mucin-like protein 1, which is expressed in heart, kidney, and placenta. We performed whole mount in situ hybridization analysis of Parm1 expression in mouse embryos between gestational days (GD) 9.5 and 12.5, which are equivalent to human gestational weeks 4-6. Since the spatio-temporal localization of Parm1 corresponded to tissues which are affected in human epispadias, we sequenced PARM1 in 24 affected patients. We found Parm1 specifically expressed in the region of the developing cloaca, the umbilical cord, bladder anlage, and the urethral component of the genital tubercle. Additionally, Parm1 expression was detected in the muscle progenitor cells of the somites and head mesenchyme. PARM1 gene analysis revealed no alterations in the coding region of any of the investigated patients. These findings suggest that PARM1 does not play a major role in the development of human epispadias. However, we cannot rule out the possibility that a larger sample size would enable detection of rare mutations in this gene.
    Gene 07/2012; 506(2):392-5. · 2.20 Impact Factor
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    ABSTRACT: We characterize the urothelium from patients with classic bladder exstrophy-epispadias complex for the expression of proteins associated with urothelial differentiation, and discuss a potential impact of urothelial phenotype on the structural and functional properties of the bladder template following bladder closure. From 2005 to 2010 bladder biopsies from 32 infants with bladder exstrophy-epispadias complex obtained at primary bladder closure were collected. After histological assessment immunochemistry was used to investigate the expression of uroplakin IIIa, cytokeratin differentiation restricted antigens CK13 and CK20, and tight junction protein claudin 4. Overall tissue morphology showed gross alterations with inflammatory, proliferative and metaplastic changes in most specimens. Sections of intact epithelium were present in 78% of biopsies. With respect to urothelial phenotype, CK13 was expressed in all specimens, whereas UPIIIa and CK20 were absent in 76% of the tissues examined. Of the biopsies 52% revealed an irregular expression pattern of tight junction protein Cl-4. This is the first study to our knowledge to characterize the urothelium from infants with bladder exstrophy-epispadias complex for the expression of urothelial differentiation associated antigens. Our findings suggest urothelial differentiation changes in a majority of exstrophic bladders, at least at primary bladder closure. Although the underlying etiology remains to be established, abnormal urothelial differentiation may result in a dysfunctional urothelial barrier with implications for the structural and functional properties of the bladder template. Despite the study limitations, our preliminary findings provide a platform for further investigation of the significance of the urothelium for the exstrophic bladder.
    The Journal of urology 03/2012; 187(5):1806-11. · 3.75 Impact Factor
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    ABSTRACT: To identify genetic and nongenetic risk factors that contribute to the severity of the bladder exstrophy-epispadias complex (BEEC). Patients with BEEC from North America (n = 167) and Europe (n = 274) were included. The following data were collected: associated anomalies, parental age at conception, mode of conception, periconceptional folic acid supplementation, maternal risk factors during pregnancy, and environmental risk factors. The patients were divided into 3 subgroups according to phenotype severity: (i) mild, epispadias (n = 43); (ii) intermediate, classic bladder exstrophy (n = 366); and (iii) severe, cloacal exstrophy (n = 31). These subgroups then were compared with identify factors that contribute to phenotype severity. Males were overrepresented in all subgroups. A relatively high prevalence of cleft lip, with or without cleft palate, was observed. Maternal smoking and medical radiation during the first trimester were associated with the severe cloacal exstrophy phenotype. Compliance with periconceptional folic acid supplementation was associated with the mildest phenotype (epispadias). Periconceptional folic acid supplementation appears to prevent the development of the severe phenotype of BEEC.
    The Journal of pediatrics 06/2011; 159(5):825-831.e1. · 4.02 Impact Factor
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    ABSTRACT: The exstrophy-epispadias complex (EEC) comprises a spectrum of urogenital anomalies in which part or all of the distal urinary tract fails to close. The present study aimed to identify microaberrations characterized by loss or gain of genomic material that contribute to the EEC at a genome-wide level. Molecular karyotyping, utilizing 549,839 single nucleotide polymorphisms (SNPs) with an average spacing of 5.7 kilobases, was performed to screen an initial cohort of 16 patients with non-syndromic EEC. A de novo microduplication involving chromosomal region 22q11.21 was identified in one patient with classic exstrophy of the bladder (CBE). Subsequent multiplex ligation-dependent probe amplification (MLPA) analysis was performed with an MLPA 22q11 kit in a further 50 non-syndromic EEC cases. We identified one CBE patient with an overlapping 22q11.21 duplication in whom the duplication had been transmitted from the unaffected mother. Chromosomal region 22q11 is well known for its susceptibility to genomic rearrangements, and these are associated with various syndromes including the velo-cardio-facial/DiGeorge syndrome (VCFS/DGS), the der(22) syndrome, and the cat-eye syndrome. Duplications in this region result in a wide and variable spectrum of clinical presentations that include features of the VCFS/DGS, while some carriers present with a completely normal phenotype. Our findings extend the phenotypic spectrum of the 22q11.2 duplication syndrome, and indicate that this aberration predisposes to CBE with incomplete penetrance.
    European journal of medical genetics 04/2010; 53(2):55-60. · 1.57 Impact Factor
  • Journal of Pediatric Urology. 01/2010; 6.
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    ABSTRACT: Exstrophy-epispadias complex (EEC) represents a spectrum of genitourinary malformations ranging in severity from epispadias (E) to classical bladder exstrophy (CEB) and exstrophy of the cloaca (EC). Depending on severity, EEC may involve the urinary system, musculoskeletal system, pelvis, pelvic floor, abdominal wall, genitalia, and sometimes the spine and anus. Prevalence at birth for the whole spectrum is reported at 1/10,000, ranging from 1/30,000 for CEB to 1/200,000 for EC, with an overall greater proportion of affected males. EEC is characterized by a visible defect of the lower abdominal wall, either with an evaginated bladder plate (CEB), or with an open urethral plate in males or a cleft in females (E). In CE, two exstrophied hemibladders, as well as omphalocele, an imperforate anus and spinal defects, can be seen after birth. EEC results from mechanical disruption or enlargement of the cloacal membrane; the timing of the rupture determines the severity of the malformation. The underlying cause remains unknown: both genetic and environmental factors are likely to play a role in the etiology of EEC. Diagnosis at birth is made on the basis of the clinical presentation but EEC may be detected prenatally by ultrasound from repeated non-visualization of a normally filled fetal bladder. Counseling should be provided to parents but, due to a favorable outcome, termination of the pregnancy is no longer recommended. Management is primarily surgical, with the main aims of obtaining secure abdominal wall closure, achieving urinary continence with preservation of renal function, and, finally, adequate cosmetic and functional genital reconstruction. Several methods for bladder reconstruction with creation of an outlet resistance during the newborn period are favored worldwide. Removal of the bladder template with complete urinary diversion to a rectal reservoir can be an alternative. After reconstructive surgery of the bladder, continence rates of about 80% are expected during childhood. Additional surgery might be needed to optimize bladder storage and emptying function. In cases of final reconstruction failure, urinary diversion should be undertaken. In puberty, genital and reproductive function are important issues. Psychosocial and psychosexual outcome depend on long-term multidisciplinary care to facilitate an adequate quality of life.
    Orphanet Journal of Rare Diseases 10/2009; 4:23. · 4.32 Impact Factor
  • Journal of Pediatric Urology. 01/2009; 5.
  • American Journal of Medical Genetics Part A 12/2007; 143A(22):2751-6. · 2.30 Impact Factor
  • American Journal of Medical Genetics Part A 12/2006; 140(22):2506-9. · 2.30 Impact Factor
  • W. Rösch, A. Ebert, G. Schott
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    ABSTRACT: Ohne Zusammenfassung
    Der Urologe 01/2006; 45. · 0.46 Impact Factor

Publication Stats

97 Citations
37.90 Total Impact Points

Institutions

  • 2013
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 2010–2013
    • University of Bonn
      • Institute of Human Genetics
      Bonn, North Rhine-Westphalia, Germany
  • 2006–2013
    • Krankenhaus Barmherzige Brüder Regensburg
      Ratisbon, Bavaria, Germany
  • 2012
    • German Cancer Research Center
      • Division of Clinical Epidemiology and Aging Research
      Heidelberg, Baden-Wuerttemberg, Germany
    • Max Planck Institute for Molecular Genetics
      • Department of Developmental Genetics
      Berlín, Berlin, Germany
  • 2009–2012
    • University Hospital Regensburg
      Ratisbon, Bavaria, Germany
  • 2006–2012
    • Universität Regensburg
      • Department of Urology
      Ratisbon, Bavaria, Germany
  • 2007
    • Hospital of St. Hedwig
      Trebnitz, Lower Silesian Voivodeship, Poland