Identification of cytogenetic abnormalities as a consequence of FMR-1 testing in schools

A pilot project utilizing saliva to identify the FMR-1 mutation in high-risk special education students from five public school districts in Colorado has been described previously. The current article reports the identification of chromosomal abnormalities in 4 students within our high-risk population. Evaluation and subsequent chromosome testing of male students with an extra X allele originally discovered through fragile X DNA testing revealed a student with a 48,XXYY male karyotype and a 47,XXY male karyotype. A 3rd student was identified with a 47,XYY male karyotype and a 4th student was identified with a 46,XX,dup(15)(q11.2→q13) female karyotype. Our project followed a specific protocol that culminated in a visit to the school in order to conduct a brief examination of the selected students' face and hands and to collect saliva for analysis of the FMR-1 mutation by polymerase chain reaction. Equivocal samples were studied by direct DNA testing using Southern blot analysis. Results suggesting the presence of the FMR-1 gene mutation were confirmed by blood analysis for the FMR-1 mutation. When the number of FMR-1 bands determined by molecular analysis differed from that expected from the reported sex, cytogenetic analysis was performed to rule out a sex chromosomal abnormality. Individuals who had abnormal results received genetic counseling and a medical assessment. Of the 478 students evaluated, 67% were male with an average of 7.65 years and 7.5% were mentally retarded or autistic. Most students referred for the evaluation were learning disabled (57%) and/or had an attention deficit hyperactivity disorder (34%). The overall yield of identified sex chromosomal abnormalities was 0.63%. The overall yield of chromosomal abnormalities was 0.84%. The prevalence of the FMR-1 gene mutation was 1.3%. The results of our project demonstrate the importance of a cytogenetic workup whenever unusual X allele patterns are found in fragile X DNA testing and for children at high risk for a genetic diagnosis, particularly if they have unusual physical features.