Non-Invasive Prenatal Test Analysis Opens a Pandora's Box: Identification of Very Rare Cases of SRY-Positive Healthy Females, Segregating for Three Generations Thanks to Preferential Inactivation of the XqYp Translocated Chromosome

The translocation of the testis-determining factor, the SRY gene, from the Y to the X chromosome is a rare event that causes abnormalities in gonadal development. In all cases of males and females carrying this translocation, disorder of sex development is reported. In our study, we described a pecu...

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Bibliographic Details
Published in:Genes 2024-01, Vol.15 (1), p.103
Main Authors: Politi, Cristina, Grillone, Katia, Nocera, Donatella, Colao, Emma, Bellisario, Michelle Li, Loddo, Sara, Catino, Giorgia, Novelli, Antonio, Perrotti, Nicola, Rodolfo, Iuliano, Malatesta, Paola
Format: Article
Language:English
Subjects:
Chromosome Aberrations
Chromosomes, Human, X - genetics
Correspondence
Counseling
DNA microarrays
Ethylenediaminetetraacetic acid
Female
Females
Genes
Genes, sry
Humans
Infertility
Karyotypes
Karyotyping
Laboratories
Lymphocytes
Male
Patients
Pregnancy
Pregnant women
Sex-Determining Region Y Protein - genetics
Testis-determining factor
Translocation, Genetic - genetics
Villus
X chromosomes
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Summary:The translocation of the testis-determining factor, the SRY gene, from the Y to the X chromosome is a rare event that causes abnormalities in gonadal development. In all cases of males and females carrying this translocation, disorder of sex development is reported. In our study, we described a peculiar pedigree with the first evidence of four healthy females from three generations who are carriers of the newly identified t(X;Y)(q28;p11.2)(SRY+) translocation with no evidence of ambiguous genitalia or other SRY-dependent alterations. Our study was a consequence of a Non-Invasive Prenatal Test (NIPT) showing a sexual chromosomal abnormality (XXY) followed by a chorionic villus analysis suggesting a normal karyotype 46,XX and t(X;Y) translocation detected by FISH. Here, we (i) demonstrated the inheritance of the translocation in the maternal lineage via karyotyping and FISH analysis; (ii) characterised the structural rearrangement via chromosomal microarray; and (iii) demonstrated, via Click-iT EdU Imaging assay, that there was an absolute preferential inactivation of the der(X) chromosome responsible for the lack of SRY expression. Overall, our study provides valuable genetic and molecular information that may lead personal and medical decisions.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes15010103