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19–22 APRIL, 2017, BARCELONA, SPAIN
S2: BASIC RESEARCH 2
Moderators: Magdalena Fossum (Sweden), Berk Burgu (Turkey)
ESPU Meeting on Wednesday 19, April 2017, 15:35–17:00
15:35–15:38
S2-1 (PP)
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MUTATIONS IN THE ISL1 GENE IN HUMAN BLADDER
EXSTROPHY
Samara ARKANI
1
, Jia CAO
1
, Johanna LUNDIN
2
, Daniel NILSSON
3
,
Thomas KÄLLMAN
4
, Gillian BARKER
5
, Gundela HOLMDAHL
6
,
Christina CLEMENTSSON KOCKUM
7
, Hans MATSSON
1
and Agneta NORDENSKJÖLD
1
1) Karolinska Institutet, Department of Women’s and Children’s Health and Center for Molecular Medicine,
Stockholm, SWEDEN - 2) Karolinska Institutet, Department of Women’s and Children’s Health, Department
of Clinical Genetics, Stockholm, SWEDEN - 3) Karolinska Institutet, 3Department of Molecular Medicine and Surgery
and Center for Molecular Medicine, Stockholm, SWEDEN - 4) Uppsala University, Science for Life Laboratory,
Department of Medical Biochemistry and Microbiology, Uppsala, SWEDEN - 5) Uppsala University, Department
of Women’s and Children’s Health, Uppsala, SWEDEN - 6) Queen Silvia Children’s Hospital, Department of Pediatric
Surgery, Gothenburg, SWEDEN - 7) University Hospital Lund, Department of Pediatric Surgery, Lund, SWEDEN
INTRODUCTION
Bladder exstrophy is a congenital closure defect of the urinary bladder with profound impact on
morbidity. Although the malformation is usually sporadic, a genetic background is supported by an
increased recurrence risk in offspring and siblings, higher concordance rates in monozygotic twins
and several associated chromosomal aberrations. Recently, ISL1 was presented as a candidate
gene in a genome wide association study for bladder exstrophy.
In this study we assessed the ISL1 mutation frequency in DNA from patients with bladder exstrophy
and evaluated the ISL1 expression in human fetal bladder during the critical time frame for the
development of bladder exstrophy and epispadia complex.
MATERIAL AND METHODS
DNA was isolated from either blood or skin from 125 patients with bladder exstrophy that were
recruited nationally by the Pediatric Surgery Departments. We sequenced coding exons in ISL1.
In the control group we used DNA from two different sources, peripheral blood from anonymous
blood donors and placenta tissue acquired after normal delivery of healthy newborns of european
origin and without any obvious malformations.
RNA sequencing of human fetal bladder tissue during fetal weeks 5-10 was compared to lung tissue
from week 9 as a control.
RESULTS
In total 17 genetic variants in ISL1 were identified including a novel missense variant,
c.137C>G p.(Ala46Gly), substituting a conserved amino acid. This variant is inherited from the
healthy mother, observation in healthy females may not exclude causation. We also detected ISL1
mRNA expression in fetal bladders during the whole period examined.
CONCLUSIONS
Our results support that mutations in ISL1 may be a rare mechanism for the development of bladder
exstrophy.