NCT01995305

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

• Status: Available
• Phase: —
• Study type: Expanded Access
• Enrollment: —
• Sponsor: Xiaofan Zhu · Unknown
• Sex: All
• Age: 1 Month – 18 Years
• Healthy volunteers: —

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.

Conditions

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

Interventions

Type	Name	Description
GENETIC	human whole exome	he exome is the part of the genome formed by exons, coding portions of genes in the genome that are used in the synthesis of proteins, therefore, it is most likely to contribute to the phenotype of an organism. The exome of the human genome, is estimated to comprise 1.5% of the total genome (The human exome is about 30 MB).
GENETIC	whole genomic	This study propose to find the genes that are sensitive to DNA crosslink repair, and genes that have key roles in hematopoietic cell development and maturation.

Timeline

• First posted: 2013-11-26
• Last updated: 2013-11-26

Locations

1 site across 1 country: China