No abstract available.
Fanconi Anemia*

No abstract available.
Fanconi Anemia*

Fanconi Anemia ; diagnosis ; therapy ; Humans

We report 1 case of Fanconi's anemia which has severe pancytopenia, PDA, hypoplatic right thumb and cryptorchism with a brief review of related literature and references.
Cryptorchidism ; Fanconi Anemia* ; Male ; Pancytopenia ; Thumb

OBJECTIVETo explore the feasibility of single-cell gel electrophoresis (SCGE) as one of lab tests to examine DNA breakage for the diagnosis of Fanconi anemia (FA). Case Record A 4-year-and-10-month old boy presented with cryptorchism, deformities of both thumbs and esotropia of right eye. He developed thrombocytopenia and anemia when he was 3 year- and -2-month old. He was clinically diagnosed as FA.

METHODS AND RESULTSDNA breakage of peripheral white blood cells from the patient and his parents was examined with SCGE. The percentages of cells with chromosome breakage (comet-tail positive cells) were 100%, 90% and 52% for the patient,his father and mother, respectively, while that were only 2% and 5% in two normal same-age children (P <0. 001). The micronucleus-positive lymphocytes was 6.74% in the patient, being also much higher than normal value (0.40%).

CONCLUSIONSCGE disclosed DNA breakage in the patient with FA, suggesting that it could be used as a test for determining DNA breakage of FA.

Child, Preschool ; Comet Assay ; Fanconi Anemia ; diagnosis ; Humans ; Male

DNA ; DNA Damage ; DNA Repair ; Fanconi Anemia/genetics* ; Humans

Bone Marrow Failure Disorders ; Fanconi Anemia/complications* ; Humans

OBJECTIVETo screen the FANCA gene mutation and explore the FANCA protein function in Fanconi anemia (FA) patients.

METHODSFANCA protein expression and its interaction with FANCF were analyzed using Western blot and immunoprecipitation in 3 cases of FA-A. Genomic DNA was used for MLPA analysis followed by sequencing.

RESULTSFANCA protein was undetectable and FANCA and FANCF protein interaction was impaired in these 3 cases of FA-A. Each case of FA-A contained biallelic pathogenic mutations in FANCA gene.

CONCLUSIONSNo functional FANCA protein was found in these 3 cases of FA-A, and intragenic deletion, frame shift and splice site mutation were the major pathogenic mutations found in FANCA gene.

Cell Line ; DNA Mutational Analysis ; Fanconi Anemia ; genetics ; metabolism ; Fanconi Anemia Complementation Group A Protein ; genetics ; metabolism ; Humans ; Mutation

OBJECTIVETo study FANCA protein expression in Fanconi anemia patient's (FA) cells and explore its function.

METHODSFANCA protein expression was analyzed in 3 lymphoblast cell lines derived from 3 cases of type A FA (FA-A) patients using Western blot. Nucleus and cytoplasm localization of FANCA protein was analyzed in one case of FA-A which contained a truncated FANCA (exon 5 deletion). The FANCA mutant was constructed from the same patient and its interaction with FANCG was evaluated by mammalian two-hybrid (M2H) assay.

RESULTSFANCA protein was not detected in the 3 FA-A patients by rabbit anti-human MoAb, but a truncated FANCA protein was detected in 1 of them by mouse anti-human MoAb. The truncated FANCA could not transport from cytoplasm into nucleus. The disease-associated FANCA mutant was defective in binding to FANCG in M2H system.

CONCLUSIONSFANCA proteins are defective in the 3 FA-A patients. Disfunction of disease-associated FANCA mutant proved to be the pathogenic mutations in FANCA gene. Exon 5 of FANCA gene was involved in the interaction between FANCA and FANCG.

Cell Line ; Child ; Exons ; Fanconi Anemia ; genetics ; metabolism ; Fanconi Anemia Complementation Group A Protein ; genetics ; metabolism ; Humans ; Lymphocytes ; metabolism ; Male ; Mutation

BACKGROUND: Fanconi's anemia (FA) is an autosomal recessive disease characterized by aplastic anemia, pre-malignancy, congenital malformations and chromosome breakage syndromes. As up to 30% of patients have no detectable congenital anomalies, the modern diagnosis of FA rests on chromosomal breakage of patient's cells induced by chemical clastogens such as diepoxybutane (DEB) or mitomycin-C (MMC). METHODS: We have done chromosome breakage test to differentiate FA from 11 aplastic anemia, three Diamond-Blackfan syndrome, three myelodysplastic syndrome, one acute leukemia with congenital anomaly and three siblings of FA. The peripheral blood lymphocytes from each individual were co-cultured in phytohemagglutinin-containing medium by the three methods, i.e., DEB treated, MMC treated and un-treated. RESULTS: Five cases were found to have increased chromosomal breakages to DEB and MMC, confirming diagnosis of FA. Other 21 cases showed no increased chromosomal breakages. No overlap was found between FA group and others (P<0.01). In one FA, there was no increased spontaneous breakage, but increased breakage to DEB and MMC. Of five FA, one case showed no congenital anomalies. CONCLUSIONS: Chromosme breakage test was shown to be simple, reliable and useful in ascertaining the diagnosis of FA.
Anemia, Aplastic ; Chromosome Breakage* ; Diagnosis* ; Fanconi Anemia* ; Humans ; Leukemia ; Lymphocytes ; Mitomycin ; Mutagens ; Myelodysplastic Syndromes ; Siblings