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Investigating the role of X chromosome breakpoints in premature ovarian failure

Simona Baronchelli1, Nicoletta Villa2, Serena Redaelli1, Sara Lissoni2, Fabiana Saccheri2, Elena Panzeri1, Donatella Conconi1, Angela Bentivegna1, Francesca Crosti2, Elena Sala2, Francesca Bertola3, Anna Marozzi4, Antonio Pedicini5, Marialuisa Ventruto5, Maria Adalgisa Police5 and Leda Dalprà12*

Author Affiliations

1 Department of Neuroscience and Biomedical Technologies, University of Milan-Bicocca, Via Cadore 48, 20900, Monza, MB, Italy

2 Medical Genetics Laboratory, S. Gerardo Hospital, Via Pergolesi 33, 20900, Monza, MB, Italy

3 Human Molecular Genetic Consortium, University of Milan-Bicocca, Via Cadore 48, 20900, Monza, MB, Italy

4 Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133, Milan, Italy

5 Medical Genetics Laboratory, S. Giuseppe Moscati Hospital, Viale Italia 1, 83100, Avellino, Italy

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Molecular Cytogenetics 2012, 5:32  doi:10.1186/1755-8166-5-32

Published: 16 July 2012


The importance of the genetic factor in the aetiology of premature ovarian failure (POF) is emphasized by the high percentage of familial cases and X chromosome abnormalities account for 10% of chromosomal aberrations. In this study, we report the detailed analysis of 4 chromosomal abnormalities involving the X chromosome and associated with POF that were detected during a screening of 269 affected women. Conventional and molecular cytogenetics were valuable tools for locating the breakpoint regions and thus the following karyotypes were defined: 46,X,der(X)t(X;19)(p21.1;q13.42)mat, 46,X,t(X;2)(q21.33;q14.3)dn, 46,X,der(X)t(X;Y)(q26.2;q11.223)mat and 46,X,t(X;13)(q13.3;q31)dn. A bioinformatic analysis of the breakpoint regions identified putative candidate genes for ovarian failure near the breakpoint regions on the X chromosome or on autosomes that were involved in the translocation event. HS6ST1, HS6ST2 and MATER genes were identified and their functions and a literature review revealed an interesting connection to the POF phenotype. Moreover, the 19q13.32 locus is associated with the age of onset of the natural menopause. These results support the position effect of the breakpoint on flanking genes, and cytogenetic techniques, in combination with bioinformatic analysis, may help to improve what is known about this puzzling disorder and its diagnostic potential.

Breakpoint definition; Premature ovarian failure; X chromosome structural aberrations