Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents

• Conditions: Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.; Hematopoiesis Maintainance.; Fanconi Anemia; Autosomal or Sex Linked Recessive Genetic Disease

• Registration Number: NCT01995305
• Lead Sponsor: Xiaofan Zhu

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2013-11
• Study First Submitted: 2013-11-21
• Study First Submitted QC: 2013-11-21
• Last Update Submitted: 2013-11-21
• Study First Posted: 2013-11-26
• Last Update Posted: 2013-11-26

Recruitment & Eligibility

• Status: AVAILABLE
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

All the children that are diagnosed to be FA patients at the Blood Disease Hospital between 08/01/2010 - 07/31/2011, will be asked to participated in this study after acquiring the consent.

Exclusion Criteria

Can not acquiring content

Study & Design

• Study Type: EXPANDED_ACCESS
• Study Design: Not specified

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, Tianjin, China