Dataset Information

Role of the LF-SINE-Derived Distal ISL1 Enhancer in Patients with Classic Bladder Exstrophy.

ABSTRACT: A genome-wide association study and meta-analysis identified ISL1 as the first genome-wide significant susceptibility gene for classic bladder exstrophy (CBE). A short interspersed repetitive element (SINE), first detected in lobe-finned fishes (LF-SINE), was shown to drive Isl1 expression in embryonic mouse genital eminence. Hence, we assumed this enhancer a conclusive target for mutations associated with CBE formation and analyzed a cohort of 200 CBE patients. Although we identified two enhancer variants in five CBE patients, their clinical significance seems unlikely, implying that sequence variants in the ISL1 LF-SINE enhancer are not frequently associated with CBE.

SUBMITTER: Zhang R

PROVIDER: S-EPMC5548531 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Role of the LF-SINE-Derived Distal ISL1 Enhancer in Patients with Classic Bladder Exstrophy.

Zhang Rong R Knapp Michael M Kause Franziska F Reutter Heiko H Ludwig Michael M

Journal of pediatric genetics 20170421 3

A genome-wide association study and meta-analysis identified ISL1 as the first genome-wide significant susceptibility gene for classic bladder exstrophy (CBE). A short interspersed repetitive element (SINE), first detected in lobe-finned fishes (LF-SINE), was shown to drive Isl1 expression in embryonic mouse genital eminence. Hence, we assumed this enhancer a conclusive target for mutations associated with CBE formation and analyzed a cohort of 200 CBE patients. Although we identif ...[more]

PMID: 28794909

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Project description:Introduction/backgroundBladder exstrophy patients have a high prevalence of inguinal hernia that often become clinically evident following bladder closure. Understanding when the bladder exstrophy patient is under greatest risk of developing an inguinal hernia following bladder closure is important, since incarceration resulting in strangulation of intra-abdominal contents can lead to significant morbidity if not addressed in a timely fashion. Although the incidence and risk factors of inguinal hernia have been reported, the timing of occurrence is not well understood.ObjectiveThe primary objective of this study was to assess the timing of inguinal hernia following complete primary repair of bladder exstrophy (CPRE). In addition, we aimed to evaluate possible risk factors associated with inguinal hernia, including sex, age at bladder closure and iliac osteotomy status.Study designA multi-institutional retrospective review identified patients with bladder exstrophy repaired by CPRE under 6 months of age while excluding those who underwent inguinal hernia repair before or during bladder closure. Timing of inguinal hernia following bladder closure was evaluated using Kaplan-Meier methods. Cox proportional hazards model was used to investigate association of sex, age at bladder closure, and osteotomy on the risk of developing of inguinal hernia while clustering for institution.Results91 subjects were included in our analysis with median follow-up time of 6.5 years. 34 of 53 males (64.2%) and 2 of 38 females (5.3%) underwent inguinal hernia repair. The median time to inguinal hernia was 4.7 months following closure. The greatest hazard of inguinal hernia was within the first six months following closure. In multivariate analysis, male sex was strongly associated with inguinal hernia (HR = 19.00, p = 0.0038). Osteotomy and delay in closure were not significantly associated with inguinal hernia. 7 of 36 patients (19.4%) who underwent inguinal hernia repair presented with recurrence on the ipsilateral side.DiscussionOur results suggest that the greatest risk of inguinal hernia is within the first six months following bladder closure. The decreased risk of inguinal hernia after one year of follow-up may reflect anatomic stability that is reached following major reconstruction of the pelvis. While male bladder exstrophy patients are significantly more susceptible to inguinal hernias following CPRE, osteotomy and delayed bladder closure do not appear to be protective factors for inguinal hernia development following initial bladder closure.ConclusionsThere is a heightened risk of inguinal hernia in the first six months following closure. The rate of recurrence following inguinal hernia repair is significantly elevated compared to the general pediatric population.

Dataset Information

Role of the LF-SINE-Derived Distal ISL1 Enhancer in Patients with Classic Bladder Exstrophy.

Publications

Role of the LF-SINE-Derived Distal <i>ISL1</i> Enhancer in Patients with Classic Bladder Exstrophy.

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