SRY+ Derivative X Chromosome in a Female With Apparently Typical Sexual Development

Area of Science:

• Genetics
• Reproductive Biology
• Prenatal Diagnosis

Background:

• The SRY gene typically dictates male sex development in 46,XY fetuses.
• Presence of SRY in a 46,XX fetus usually leads to some degree of testicular development.
• This study investigated a 46,XX fetus with positive Y chromosome screening but typical female ultrasound findings.

Purpose of the Study:

• To determine the clinical significance of Y chromosome material detected by noninvasive prenatal screening (NIPS) in a 46,XX fetus.
• To investigate the genetic basis for typical female development despite the presence of Y chromosome material.

Main Methods:

• Prenatal genetic analysis of fetal material via amniocentesis.
• Techniques included G-banding, microarray, fluorescence in situ hybridization (FISH), and optical genome mapping (OGM).

Main Results:

• G-banding confirmed a normal 46,XX karyotype.
• Microarray and FISH identified an SRY-positive (SRY+) translocation of Yp material to Xq, with a concurrent deletion of Xq.
• The resulting karyotype was 46,X,der(X)t(X;Y)(q28;p11.2), with deletion of the IKBKG gene.
• Prenatal ultrasound and postnatal examination showed typical female genitalia.
• OGM software did not directly identify the translocation.

Conclusions:

• This case highlights that the SRY gene can be present in a 46,XX individual with typical female development.
• Preferential inactivation of the derivative X chromosome, carrying the SRY translocation and IKBKG deletion, likely explains the normal female phenotype.
• This finding underscores the complexity of sex determination and the importance of comprehensive genetic analysis.