Fate of SRY, PABY, DYS1, DYZ3 and DYZ1 loci in Indian patients harbouring sex chromosomal anomalies

Abstract

We analysed chromosomes, conducted hormonal assays and screened genomic DNA of 34 patients with or without detectable Y chromosome for the presence/absence of SRY, PABY, DYS1, DYZ3 and DYZ1 loci and for mutations in the SRY gene. The samples studied represented cases of oligozoospermia, cryptorchidism, Swyer syndrome, Turner syndrome, male pseudohermaphroditism, XXY female syndrome, Klinefelter's syndrome, repeated abortion and instances of male infertility. Chromosomal constitutions and the level of hormones (FSH, LH, PRL, E2 and TSH) were found to be abnormal in several cases. A phenotypic female (P20) positive for all the Y-linked loci screened, showed mutations upstream of the HMG box in the SRY gene. In addition, one or more of the Y-linked loci were detected in several phenotypic females. Fluorescence in-situ hybridization of metaphase chromosomes and interphase nuclei of an aborted fetus with DYZ1 probe detected signals from normal to low levels to its complete absence confirming a complex Y chromosome mosaicism. Upon DNA analysis, the fetus was found to be positive for all the above-mentioned Y-linked loci. Organizational variation within the DYZ1 arrays and its correlation with recurrent spontaneous abortion may be followed-up in subsequent studies to substantiate this observation. This would augment genetic counselling to the affected couples. Prospects of this approach in the overall management of clinical cases with sex chromosome-related anomalies are discussed.