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

doi:10.1056/NEJMoa1800024

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

75 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 language	English
Pages (from-to)	1042-1049
Number of pages	8
Journal	New England Journal of Medicine
Volume	379
Issue number	11
DOIs	https://doi.org/10.1056/NEJMoa1800024
State	Published - 13 Sep 2018

Funding

Funders	Funder number
Shaare Zedek Medical Center
National Institutes of Health	1353/12
National Cancer Institute	R35CA197458
Breast Cancer Research Foundation
Legacy Heritage Fund	1788/15
Hadassah Medical Organization
Israel Science Foundation

UN SDGs

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Weinberg-Shukron, A., Rachmiel, M., Renbaum, P., Gulsuner, S., Walsh, T., Lobel, O., Dreifuss, A., Ben-Moshe, A., Zeligson, S., Segel, R., Shore, T., Kalifa, R., Goldberg, M., King, M. C., Gerlitz, O., Levy-Lahad, E., & Zangen, D. (2018). Essential Role of BRCA2 in Ovarian Development and Function. New England Journal of Medicine, 379(11), 1042-1049. https://doi.org/10.1056/NEJMoa1800024

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title = "Essential Role of BRCA2 in Ovarian Development and Function",

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.",

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

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doi = "10.1056/NEJMoa1800024",

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Weinberg-Shukron, A, Rachmiel, M, Renbaum, P, Gulsuner, S, Walsh, T, Lobel, O, Dreifuss, A, Ben-Moshe, A, Zeligson, S, Segel, R, Shore, T, Kalifa, R, Goldberg, M, King, MC, Gerlitz, O, Levy-Lahad, E & Zangen, D 2018, 'Essential Role of BRCA2 in Ovarian Development and Function', New England Journal of Medicine, vol. 379, no. 11, pp. 1042-1049. https://doi.org/10.1056/NEJMoa1800024

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AU - Rachmiel, Mariana

AU - Renbaum, Paul

AU - Gulsuner, Suleyman

AU - Walsh, Tom

AU - Lobel, Orit

AU - Dreifuss, Amatzia

AU - Ben-Moshe, Avital

AU - Zeligson, Sharon

AU - Segel, Reeval

AU - Shore, Tikva

AU - Kalifa, Rachel

AU - Goldberg, Michal

AU - King, Mary Claire

AU - Gerlitz, Offer

AU - Levy-Lahad, Ephrat

AU - Zangen, David

PY - 2018/9/13

Y1 - 2018/9/13

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AB - 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.

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Essential Role of BRCA2 in Ovarian Development and Function

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