Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations

Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations

Author Moyses-Oliveira, Mariana Autor UNIFESP Google Scholar
Guilherme, Roberta dos Santos Autor UNIFESP Google Scholar
Dantas, Anelisa Gollo Autor UNIFESP Google Scholar
Ueta, Renata Autor UNIFESP Google Scholar
Perez, Ana Beatriz Autor UNIFESP Google Scholar
Haidar, Mauro Abi Autor UNIFESP Google Scholar
Canonaco, Rosane Google Scholar
Meloni, Vera Ayres Autor UNIFESP Google Scholar
Kosyakova, Nadezda Google Scholar
Liehr, Thomas Google Scholar
Carvalheira, Gianna Maria Autor UNIFESP Google Scholar
Melaragno, Maria Isabel Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Hosp Servidor Publ Estado São Paulo
Univ Jena
Abstract Objective: To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility.Design: Retrospective and case-control study.Setting: University-based research laboratory.Patient(s): Three women with balanced X-autosome translocation and primary amenorrhea.Intervention(s): Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction.Main Outcome Measure(s): Karyotype, copy number variation, breakpoint mapping, and gene expression levels.Result(s): All patients presented with breakpoints in the Xq13q21 region. in two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. the ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. the break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. in the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. the FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region.Conclusion(s): the etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. the fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea. (C) 2015 by American Society for Reproductive Medicine.
Keywords X-chromosome
reciprocal translocation
female fertility
primary amenorrhea
position effect
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2011/51690-1
Date 2015-05-01
Published in Fertility and Sterility. New York: Elsevier B.V., v. 103, n. 5, p. 1289-+, 2015.
ISSN 0015-0282 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1289-+
Access rights Closed access
Type Article
Web of Science ID WOS:000353843700033

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