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

Rong Zhang; Michael Knapp; Franziska Kause; Heiko Reutter; Michael Ludwig

doi:10.1055/s-0037-1602387

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

J Pediatr Genet. 2017 Sep;6(3):169-173. doi: 10.1055/s-0037-1602387. Epub 2017 Apr 21.

Authors

Rong Zhang¹, Michael Knapp², Franziska Kause¹, Heiko Reutter^{1

3}, Michael Ludwig⁴

Affiliations

¹ Institute of Human Genetics, University of Bonn, Bonn, Germany.
² Institute of Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany.
³ Department of Neonatology and Pediatric Intensive Care, Children's Hospital, University of Bonn, Bonn, Germany.
⁴ Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.

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.

Keywords: ISL1; LF-SINE; cis -regulatory element; classic bladder exstrophy; enhancer.