Essential Role of BRCA2 in Ovarian Development and Function

Ariella Weinberg-Shukron, Mariana Rachmiel, Paul Renbaum, Suleyman Gulsuner, Tom Walsh, Orit Lobel, Amatzia Dreifuss, Avital Ben-Moshe, Sharon Zeligson, Reeval Segel, Tikva Shore, Rachel Kalifa, Michal Goldberg, Mary Claire King, Offer Gerlitz, Ephrat Levy-Lahad, David Zangen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

The causes of ovarian dysgenesis remain incompletely understood. Two sisters with XX ovarian dysgenesis carried compound heterozygous truncating mutations in the BRCA2 gene that led to reduced BRCA2 protein levels and an impaired response to DNA damage, which resulted in chromosomal breakage and the failure of RAD51 to be recruited to double-stranded DNA breaks. The sisters also had microcephaly, and one sister was in long-term remission from leukemia, which had been diagnosed when she was 5 years old. Drosophila mutants that were null for an orthologue of BRCA2 were sterile, and gonadal dysgenesis was present in both sexes. These results revealed a new role for BRCA2 and highlight the importance to ovarian development of genes that are critical for recombination during meiosis.

Original languageAmerican English
Pages (from-to)1042-1049
Number of pages8
JournalNew England Journal of Medicine
Volume379
Issue number11
DOIs
StatePublished - 13 Sep 2018

Bibliographical note

Publisher Copyright:
Copyright © 2018 Massachusetts Medical Society.

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