0000000000125286
AUTHOR
Lars Wittler
SLC20A1 Is Involved in Urinary Tract and Urorectal Development
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exs…
Murine expression and mutation analyses of the prostate androgen-regulated mucin-like protein 1 (Parm1) gene, a candidate for human epispadias.
Abstract Background 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. Methods 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 e…
Isolated bladder exstrophy associated with a de novo 0.9 Mb microduplication on chromosome 19p13.12
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 mutati…
Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region
Background: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients. Methods: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls. Results: New duplications of …
Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder
Item does not contain fulltext Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our disc…