PHENOTYPE-GENOTYPE AND PEDIGREE ANALYSIS OF ISOLATED HYPOSPADIAS PATIENTS
Abstract: Hypospadias is a
malformation in urethra which has many range of severity. A patient with
Isolated hypospadias (IH), a mild disorder of sex development (DSD) has a
hypospadias phenotype only. Hypospadias is considered as multifactorial disease
in which genetic factors contribute to its development. Chromosome analysis in
DSD including hypospadias is conducted for gender assignment and other possible
genetic contributions. This analysis solely could not elucidate all genetic
causes of hypospadias. Polymorphism of V89L in SRD5A2 is suggested as one of
genetic risk factors of hypospadias. To determine the genetic risk factor and
pattern of inheritance, a good pedigree construction is required. Material
& methods: 35 eligible subjects with IH admitted to Center for Biomedical
Research (CEBIOR) during 2012-2015 were randomly selected. 35 normal male as
control were included in this study. Data on three generation pedigrees were
collected from medical records in 35 affected subjects. Chromosome analyses
were done by using G-banding technique. Polymorphism analysis of V89L in SRD5A2
gene was done using PCR-RFLP technique in all samples. Results: From the 35
affected subjects, the most frequent phenotype was penile hypospadias (47%), a
pair of twins were monozygotic and one had a cousin diagnosed with urogenital
abnormalities (i.e micropenis and chordae). All subjects had 46,XY chromosome.
No chromosomal aberration was found. No positive correlation between
polymorphism of V89L in SRD5A2 and risk of hypospadias (PR of CC+CG vs GG=1.0,
95% CI: 0.342−2.921, p value=1.0). Conclusion: The pedigree data from our study
implies tendency of genetic involvement in hypospadias cases. There were no
chromosomal aberrations in hypospadias cases. The finding on polymorphism of
V89L in SRD5A2 gene does not support that of previous studies.
Keywords: Pedigree;
hypospadias; risk factor; SRD5A2
Author: Nura Eky Vikawati,
Ardy Santosa, Achmad Zulfa Juniarto, Sultana MH Faradz
Journal Code: jpkedokterangg180006
