Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents
Fanconi anemia is a rare autosomal or sex linked recessive genetic disease. The disease is characterized by bone marrow hematopoiesis failure, multiple congenital abnormalities, and susceptibility to neoplastic diseases. The cells of FA patients are extremely sensitive to MMC and DEB. The symptoms and ages of FA patients are different, so by comparing the exome of FA patients and their parents, the mutations that were accumulated in FA patients could be found, and these genes might be sensitive to repairment and be important for hematopoiesis maintainance.
Autosomal or Sex Linked Recessive Genetic Disease
Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.
Genetic: human whole exome
Genetic: whole genomic
|Study Type:||Expanded Access What is Expanded Access?|
|Official Title:||Exome Sequencing of Fanconi Anemia Children and the Their Parents|
Genetic: human whole exome
Heterogeneity of FA. In the research of animal model, the phenotypes of FANCA, FANCC and FANCG knockout mice are similar. They grow up and develop normally, without any severe blood disease or tumor. However, they show chromosome instablity and highly sensitivity to MMC. And they have gonadal dysfunction and fertility defects. From this we conclude that the severe physical deformity of FA patients might be induced by other mutations. By comparing among the FA patients and between FA patiens and normal people, we look forward to find the mutated genes and verify their relationship with the physical deformity.
Even in 90% of FA patients the bone marrow failure will eventually occur, but the starting age ranges from 8-84. And Immuno-inhibition therapy has no effects on FA. Other DNA repair dysfunction diseases have higher rate of tumor, but not so high rate of bone marrow failure as FA does, which implies that the FA protein has the key role in hematopoietic stem cell maintainance. In FancC-/- mice, young mice is insensitive to DNA crosslinks with comet assay, but not adult mice, indicating that the accumulation of DNA damage during time leads to DNA repairment defects. by comparing the exome of FA patients and their parents, the mutations that were accumulated in FA patients could be found, and these genes might be sensitive to repairment and be important for hematopoiesis maintainance.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01995305
|Contact: Xiaofan Zhu, email@example.com|
|Contact: Huimin Zeng, firstname.lastname@example.org|
|Institute of Hematology & Blood Diseases Hospital|
|Tianjin, Tianjin, China, 300020|
|Contact: Xiaofan Zhu, professor +86-022-23909001 email@example.com|
|Principal Investigator: Xiaofan Zhu, professor|
|Principal Investigator:||Tao Cheng, professor||Institute of Hematology & Blood Diseases Hospital|