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

Exome Sequencing of Fanconi Anemia Children and the Their Parents

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.

Study Overview

• Status: Available
• Conditions: Fanconi Anemia; Autosomal or Sex Linked Recessive Genetic Disease; Bone Marrow Hematopoiesis Failure, Multiple Congenital Abnormalities, and Susceptibility to Neoplastic Diseases.; Hematopoiesis Maintainance.
• Intervention / Treatment: Genetic: human whole exome; Genetic: whole genomic

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 Type: Expanded Access

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Available
      • Institute of Hematology & Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Xiaofan Zhu
• Investigators: Principal Investigator: Tao Cheng, professor, Institute of Hematology & Blood Diseases Hospital

Publications and helpful links

Helpful Links

• informatin about this study

Study record dates

Study Registration Dates

• First Submitted: November 21, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): November 26, 2013
• Last Update Submitted That Met QC Criteria: November 21, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: fanconi anemia; hematopoiesis maintainance
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Neoplasms; Congenital Abnormalities; Anemia; Fanconi Syndrome; Fanconi Anemia; Genetic Diseases, Inborn; Abnormalities, Multiple
• Other Study ID Numbers: pumc001; zhm001 (Other Identifier: pumc)