2. Academic Validation
  3. CSB-PGBD3 Mutations Cause Premature Ovarian Failure

CSB-PGBD3 Mutations Cause Premature Ovarian Failure

  • PLoS Genet. 2015 Jul 28;11(7):e1005419. doi: 10.1371/journal.pgen.1005419.
Yingying Qin 1,  Ting Guo 1,  Guangyu Li 1,  Tie-Shan Tang 2,  Shidou Zhao 1,  Xue Jiao 1,  Juanjuan Gong 2,  Fei Gao 3,  Caixia Guo 4,  Joe Leigh Simpson 5,  Zi-Jiang Chen 6
Affiliations

Affiliations

  • 1 Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China.
  • 2 State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • 4 Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
  • 5 Research and Global Programs March of Dimes Foundation, White Plains, New York, United States of America.
  • 6 Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China; Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 26218421 DOI: 10.1371/journal.pgen.1005419
Abstract

Premature ovarian failure (POF) is a rare, heterogeneous disorder characterized by cessation of menstruation occurring before the age of 40 years. Genetic etiology is responsible for perhaps 25% of cases, but most cases are sporadic and unexplained. In this study, through whole exome Sequencing in a non-consanguineous family having four affected members with POF and Sanger Sequencing in 432 sporadic cases, we identified three novel mutations in the fusion gene CSB-PGBD3. Subsequently functional studies suggest that mutated CSB-PGBD3 fusion protein was impaired in response to DNA damage, as indicated by delayed or absent recruitment to damaged sites. Our data provide the first evidence that mutations in the CSB-PGBD3 fusion protein can cause human disease, even in the presence of functional CSB, thus potentially explaining conservation of the fusion protein for 43 My since marmoset. The localization of the CSB-PGBD3 fusion protein to UVA-induced nuclear DNA repair foci further suggests that the CSB-PGBD3 fusion protein, like many Other proteins that can cause POF, modulates or participates in DNA repair.

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