Unusual Pattern of Bone Marrow Somatic Mutation in Pediatric Patients Referred for Cytogenetic Analysis
Balkan Journal of Medical Genetics
Publication Date / Copyright Date
Bone marrow somatic mutation frequency, as measured by the glycophorin A (GPA) assay in circulating red blood cells, has been found to be increased in some hereditable disease syndromes associated with constitutional malformation, mental retardation, cancer susceptibility and premature aging. Increased spontaneous GPA mutation frequency has been shown to be diagnostic for ataxia telangiectasia (AT) and Fanconi’s anemia (FA). We have applied the GPA assay to a 11 pediatric patients referred for cytogenetic analysis for a variety of reasons, including developmental delay and dysmorphology. There was no evidence of any cytogenetic abnormality in these patients, so we investigated the possible role of constitutive genomic instability expressed as a high frequency of bone marrow somatic mutation. These patients had normal overall levels of GPA somatic mutation when compared to newborn and pediatric controls. When phenotypic subsets of mutants were considered, however, the patients had decreased levels of simple allele loss mutation and increased levels of allele loss and duplication. Such a shift in types of mutation without an accompanying increase in overall mutation is difficult to understand, but may be related to inherent cytotoxic susceptibility and cellular inviability in this heterogeneous patient population.
Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy
Grant, Stephen G.; McLoughlin, Reagan K.; and Wenger, Sharon L., "Unusual Pattern of Bone Marrow Somatic Mutation in Pediatric Patients Referred for Cytogenetic Analysis" (2005). Faculty Articles. 1426.