Use of the Glycophorin A Bone Marrow Somatic Mutation Assay for Rapid, Unambiguous Identification of Fanconi anemia Homozygotes Regardless of GPA Genotype
ISBN or ISSN
American Journal of Medical Genetics
Publication Date / Copyright Date
A 7-year-old girl was hospitalized with pancytopenia requiring blood transfusion. She and an older brother with suspicious symptoms were referred for laboratory testing to confirm a clinical diagnosis of Fanconi anemia (FA). Blood samples from these two children and one parent were examined with the GPA somatic mutation assay. The patient's total GPA somatic mutation frequency of 1.4 x 10(-4) was determined despite the confounding effects of her recent transfusion, and was greater than 10-fold higher than that of a population of pediatric controls, consistent with the known FA phenotype. Her brother was not informative for the standard GPA assay, which requires heterozygosity for the MN blood group, but was analyzed with a modified assay that measured only allele loss mutation. His mutation frequency, 6.8 x 10(-4) was also supportive of a diagnosis of FA. Both analyses also showed evidence of ongoing mutation through terminal erythroblast differentiation, a characteristic of patients with DNA repair syndromes which further confirmed the diagnoses. These conclusions were confirmed with traditional DEB-induced chromosome breakage studies. The quantitative and qualitative aspects of the GPA assay relevant for applying this test for FA diagnosis, and perhaps for carrier detection, are discussed.
Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy
Evdokimova, Viktoria N.; McLoughlin, Reagan K.; Wenger, Sharon L.; and Grant, Stephen G., "Use of the Glycophorin A Bone Marrow Somatic Mutation Assay for Rapid, Unambiguous Identification of Fanconi anemia Homozygotes Regardless of GPA Genotype" (2005). Faculty Articles. 1437.