Molecular Cytogenetics

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X-chromosome terminal deletion in a female with premature ovarian failure: Haploinsufficiency of X-linked genes as a possible explanation

Susana I Ferreira1, Eunice Matoso4,1, Marta Pinto1, Joana Almeida2, Thomas Liehr3, Joana B Melo1,5 and Isabel M Carreira4,1,5*

Author Affiliations

1 Laboratório de Citogenética, Instituto de Biologia Médica, Faculdade de Medicina, Universidade de Coimbra, 3000-354 Coimbra, Portugal

2 Serviço de Ginecologia, Maternidade Bissaya Barreto, 3000-061 Coimbra, Portugal

3 Jena University Hospital, Institute of Human Genetics and Anthropology, D-007740 Jena, Germany

4 CIMAGO, Universidade de Coimbra, 3001-301 Coimbra, Portugal

5 Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3000-354 Coimbra, Portugal

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Molecular Cytogenetics 2010, 3:14 doi:10.1186/1755-8166-3-14

Published: 20 July 2010

Abstract

Background

Premature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions. FMR1 gene premutation allele's carrier women have an increased risk for POF. We intent to determine the cause of POF in a 29 year old female, evaluating both of these situations.

Methods

Concomitant analysis of FMR1 gene CGG repeat number and karyotype revealed an X-chromosome terminal deletion. Fluorescence in situ further characterized the breakpoint. A methylation assay for FMR1 gene allowed to determine its methylation status, and hence, the methylation status of the normal X-chromosome.

Results

We report a POF patient with a 46,X,del(X)(q26) karyotype and with skewed X-chromosome inactivation of the structural abnormal X-chromosome.

Conclusions

Despite the hemizygosity of FMR1 gene, the patient does not present Fragile X syndrome features, since the normal X-chromosome is not subject to methylation. The described deletion supports the hypothesis that haploinsufficiency of X-linked genes can be on the basis of POF, and special attention should be paid to X-linked genes in region Xq28 since they escape inactivation and might have a role in this disorder. A full clinical and cytogenetic characterization of all POF cases is important to highlight a pattern and help to understand which genes are crucial for normal ovarian development.