[Genetic analysis of two patients with isodicentric Y chromosomes]

To investigate the karyotypic characteristics of two patients with suspected Y chromosome structural abnormalities and analyze their cytogenetic and molecular genetic findings.

Two patients who presented at the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army of China for primary amenorrhea and severe oligoasthenoteratozoospermia in April 2024 and January 2025 were enrolled, and their clinical data were collected. Peripheral blood samples were collected from each patient, and genome DNA was extracted. Chromosomal karyotypes of lymphocytes were analyzed by G- and C-banding. Multiplex fluorescence PCR was used to detect microdeletions of the SRY and AZF genes, and fluorescence in situ hybridization (FISH) was used to detect the centromeric region of Y chromosome in Patient 1 and the telomeric region in Patient 2. Multiplex ligation-dependent probe amplification (MLPA) was carried out to detect copy number variations of key genes on the Y chromosome of Patient 1, and single nucleotide polymorphism microarray (SNP array) analysis was conducted to examine genome-wide copy number variations in Patient 2. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2024-014).

Patient 1 was a 24-year-old female who presented with primary amenorrhea and elevated follicle-stimulating (FSH) and luteinizing hormone (LH) levels. Patient 2 was a 34-year-old male whom was diagnosed with severe oligoasthenoteratozoospermia after two years of infertility. For Patient 1, G- and C-banding initially identified her karyotype as 47,XX,+mar; Y chromosome microdeletion analysis indicated SRY gene deletion; MLPA revealed SRY deletion with duplication of many other genes. FISH further confirmed her karyotype as 47,XX,+mar.ish psu idic(Y)(p11.2)(DYZ3++)[44]/47,XX,+i(Y)(q10).ish i(Y)(DYZ3+)[6]. For Patient 2, SNP array revealed a 22.7 Mb gain (1-2 copies) in the Yp11.2q11.23 region. G- and C-banding initially identified his karyotype as 46,X,psu idic(Y)(q12). Microdeletion analysis showed no deletion in the SRY gene or the AZFa/b/c regions. FISH further confirmed his karyotype as 46,X,psu idic(Y)(q12).ish idic(Y)(q12)(XYp++)[20].

Combined application of multiple cytogenetic and molecular genetic techniques can facilitate accurate diagnosis of complex chromosomal abnormalities and provide reliable clues for genetic counseling and clinical intervention.