Fanconi anemia (FA) is a rare genetic disorder affecting multiple body systems. Genetic testing, including prenatal testing, is a prerequisite for the diagnosis of many clinical conditions. However, genetic testing is complicated for FA because there are often many genes that are associated with its development, and large deletions, duplications, or sequence variations are frequently found in some of these genes. This study describes successful genetic testing for molecular diagnosis, and subsequent prenatal diagnosis, of FA in a patient and his family in Korea. We analyzed all exons and flanking regions of the FANCA, FANCC, and FANCG genes for mutation identification and subsequent prenatal diagnosis. Multiplex ligation-dependent probe amplification analysis was performed to detect large deletions or duplications in the FANCA gene. Molecular analysis revealed two mutations in the FANCA gene: a frameshift mutation c.2546delC and a novel splice-site mutation c.3627-1G>A. The FANCA mutations were separately inherited from each parent, c.2546delC was derived from the father, whereas c.3627-1G>A originated from the mother. The amniotic fluid cells were c.3627-1G>A heterozygotes, suggesting that the fetus was unaffected. This is the first report of genetic testing that was successfully applied to molecular diagnosis of a patient and subsequent prenatal diagnosis of FA in a family in Korea.
Base Sequence ; Child, Preschool ; Exons ; Fanconi Anemia/*diagnosis/genetics ; Fanconi Anemia Complementation Group A Protein/genetics ; Fanconi Anemia Complementation Group C Protein/genetics ; Fanconi Anemia Complementation Group G Protein/genetics ; Female ; Frameshift Mutation ; Genetic Testing ; Heterozygote ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; RNA Splice Sites ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA

Fanconi anaemia (FA) is an autosomal recessive inherited disorder caused by defects in hematopoietic stem cells. The clinical manifestations of FA are diverse and complicated. FA cells display high hypersensitivity to agents which produce interstrand DNA cross-links such as mitomycin C (MMC) or diepoxybutane (DEB). At least eight complementation groups with defects in eight genes (FANCA, FANCB, FANCC, FANCD(1), FANCD(2), FANCE, FANCF and FANCG) have been identified by gene analysis. Six genes (corresponding to subtypes A, C, D(2), E, F and G) have been coloned, and the encoded FA proteins interact in a common cellular pathway - "FA Pathway", through which modulate DNA repair. The progress of research on FA molecular mechanism provides gene therapy of FA with theory basis. FA cells transduced with the use of retrovirus carring the normal FA gene cDNA manifestate phenotypic correction of hypersensitivity to DNA cross-linking agents, such as MMC. In this review the clinical manifestations and gene composition of FA, and the functions of encoded FA proteins were summarized. The hematopoietic stem cell transplantation and gene therapy for FA patients were discussed.
Cell Cycle Proteins ; DNA-Binding Proteins ; Fanconi Anemia ; genetics ; metabolism ; therapy ; Fanconi Anemia Complementation Group C Protein ; Fanconi Anemia Complementation Group D2 Protein ; Fanconi Anemia Complementation Group Proteins ; Genetic Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Mutation ; Nuclear Proteins ; genetics ; Proteins ; analysis ; genetics