Case Report: Prenatal genetic analysis of a rare fetus with 45, X/46, X, dic r (Y; Y)/46, X, r(Y) karyotype.

OBJECTIVE: To perform a genetic analysis of a rare complex chimeric fetus with a 45,X/46,X,dic r(Y; Y)/46,X,r(Y) karyotype, indicated by NIPT as having sex chromosome abnormalities but with normal ultrasound findings. This study underscores the critical role of integrating multiple molecular cytogenetic techniques in deciphering such complex cases, which is essential for accurate prognosis and personalized genetic counseling. The findings aim to deepen the understanding of genotype-phenotype correlations in rare chromosomal mosaicism and to guide clinical management.

METHOD: Amniotic fluid was collected from a pregnant woman with an abnormal sex chromosome indicated by NIPT. Combined detection using G-banding karyotype analysis, fluorescence in situ hybridization (FISH), and low-depth whole-genome copy number variation sequencing (CNV-seq) techniques was performed. Simultaneously collect peripheral blood samples from the fetus's parents for CNV-seq detection and paternal chromosomal karyotype analysis. The infant underwent comprehensive postnatal follow-up, including physical examination, growth assessment, developmental screening, sex hormone profiling, Y chromosome microdeletion testing, and scrotal ultrasound at 19 months of age.

RESULT: The male fetus was confirmed to have a complex karyotype through combined analysis of chromosomal G-band technology, FISH, and CNV-seq. The findings included a dicentric ring Y chromosome with mosaicism for Yp and Yq deletions, as well as a 1.40 Mb duplication in the 7q11.23 region, resulting in the karyotype: 45,X[82]/46,X,dic r(Y; Y)(p11.31q11.23; p11.31q11.23)[13]/46,X,r(Y)(p11.31q11.23) [5]dn. The father's karyotype was normal, suggesting a de novo mutation. Maternal CNV-seq was normal, while paternal CNV-seq identified the same 1.40 Mb 7q11.23 duplication, indicating paternal inheritance of this pathogenic variant. After genetic counseling, the parents proceeded with the pregnancy. On 27 June 2024, at 35+5 weeks of gestation, they gave birth to a live male infant naturally, with a length of 48 cm and a weight of 2800 g. No obvious abnormalities were observed in the appearance.

CONCLUSION: The integration of G-banding, FISH, and CNV-seq enables accurate diagnosis of complex ring Y chromosome mosaicism, providing crucial information for genetic counseling and clinical management. The clinical phenotype depends on the ring chromosome's structure, breakpoints, and the degree of mosaicism.