SPERM DNA ANALYSIS IN A FRIEDREICH ATAXIA PREMUTATION CARRIER SUGGESTS BOTH MEIOTIC AND MITOTIC EXPANSION IN THE FRDA GENE

Friedreich ataxia is usually caused by an expansion of a GAA trinucleo tide repeat in intron 1 of the FRDA gene. Occasionally, a fully expand ed allele has been found to arise from a premutation of 100 or less tr iplet repeats. We have examined the sperm DNA of a premutation carrier . This man's leucocyte DNA showed one normal allele and one allele of approximately 100 repeats. His sperm showed an expanded allele in a ti ght range centering on a size of approximately 320 trinucleotide repea ts. His affected son has repeat sizes of 1040 and 540. These data sugg est that expansion occurs in two stages, the first during meiosis foll owed by a second mitotic expansion. We also show that in all informati ve carrier father to affected child transmissions, with the notable ex ception of the premutation carrier, the expansion size decreases.