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28
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CONGRESS OF THE ESPU
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S1-2 (PP)
TWO NEW VARIANTS IN BMP7 PRODOMAIN IN TWO
PAIRS OF MONOZYGOTIC CONCORDANT TWINS
WITH HYPOSPADIAS
Aurore BOUTY
1
, Katie AYERS
2
, Ardy SANTOSA
3
, Yves HELOURY
4
, Sultana FARADZ
5
and Andrew SINCLAIR
2
1) Royal Children’s Hospital, *Urology, Parkville, AUSTRALIA - 2) MCRI, Molecular Development, Parkville, AUSTRALIA
- 3) Doctor Kariadi Hospital, Urology, Semarang, INDONESIA - 4) RCH, Urology, Parkville, AUSTRALIA - 5) Faculty
of Medicine Diponegoro University (FMDU), Centre for Biomedical Research, Semarang, INDONESIA
PURPOSE
Hypospadias is thought to be caused by a combination of genetic and environmental factors.
Variants in Bone Morphogenetic Protein 7 (BMP7) have been reported in patients with hypospadias.
Here we report two new variants in BMP7 in two pairs of twins from Indonesia.
MATERIAL AND METHODS
Patients with hypospadias were prospectively recruited in local and international clinics. After
informed consent DNA was extracted from blood. The coding regions of 1034 genes (including
64 known diagnostic and suspected candidate genes for DSD) were sequenced using a targeted
capture approach (Haloplex, Agilent), combined with massively parallel sequencing (MPS). The
resulting variants were filtered for rarity in the general population (<1%), and in our screen. Quality,
depth of the reads and predicted pathogenicity were also considered.
RESULTS
We have currently analysed sequencing from 46 hypospadias patients. Two previously unreported
variants in BMP7 were identified in two pairs of monozygotic concordant twins exhibiting proximal
hypospadias. Both variants (c.G6344, p.D212N and c.G265T, p.A89S) are heterozygous, non-
synonymous coding and affect highly conserved amino-acids in the prodomain of BMP7, a region
known to be important for the excretion of the protein in the extracellular matrix.
CONCLUSIONS
Through our targeted DSD panel we have identified two new variants in the prodomain of BMP7
in hypospadias. This region has been associated with other diseases in humans but never with
hypospadias.
Further analysis of patients with hypospadias, especially trios (patients and parents), may uncover
more novel variants that cause this DSD.