Novel mosaic SRY gene deletions in three newborn males with variable genitourinary malformations

Abstract

Ambiguous genitalia in the newborn can present a diagnostic challenge in medical practice. In most cases, the causes of genitourinary anomalies are not well understood; both genetic and environmental factors are thought to play a role. In this study, we report mosaic SRY gene deletion identified by fluorescence in situ hybridization (FISH) analysis in three unrelated newborn male patients with genital anomalies. G-banded chromosomes and microarray analysis were normal for all three patients. One patient had microphallus, hypospadias, bifid scrotum, exstrophic perineal tissue identified as a rectal duplication, lumbar vertebral anomalies, scoliosis, and a dysmorphic sacrum. The other two patients had isolated epispadias with the urethral meatus close to the penopubic junction. All three had bilateral palpable gonads in the scrotum. While this is the first report of mosaic SRY deletions, mosaic SRY sequence variants have been described in patients with variable genitourinary anomalies. This study identifies FISH analysis as a reliable method for mosaic SRY deletion detection. We suggest SRY FISH analysis should be used in the clinical workup of patients with genitourinary ambiguity.

Clinical and molecular cytogenetic findings and pregnancy outcomes of fetuses with isochromosome Y

“…Jie Xu et al found that > 20% of G-banded amniocytes with idic Yp seemed to correlate with phenotypically healthy males in most cases in the absence of other indicators of fetal structural anomalies [ 44 ]. High levels of the mosaicism of 45,X and low levels of idic(Y)/i(Y) cell lines in gonads may lead to mosaic loss, the haploinsufficiency of SRY , and an inability to maintain normal testosterone differentiation, thus manifesting in ambiguous genitalia or a female phenotype [ 45 – 48 ]. However, a lack of correlation between the level of mosaicism in AF cells and the phenotypic sex has been reported [ 49 – 51 ].…”