Clinical trial NCT01995305: Use Massive Parallel Sequencing and Exome Capture Technology to Sequence the Exome of Fanconi Anemia Children and Their Patents
Official title: Exome Sequencing of Fanconi Anemia Children and the Their Parents
Study type: EXPANDED_ACCESS
Overall 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.
Keywords: fanconi anemia
hematopoiesis maintainance
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2013-11-26
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Tao Cheng, professor
role: PRINCIPAL_INVESTIGATOR
References: