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6

28

TH

CONGRESS OF THE ESPU

13:33–13:36

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.