Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis

Facioscapulohumeral muscular dystrophy is caused by partial deletion of the D4Z4 repeat array on chromosome 4q35. Genetic diagnosis is based on sizing of this repeat array, which is complicated by cross-hybridization of a hom ologous polymorphic repeat array on chromosome 10 and by the frequent excha nges between these chromosomal regions. The restriction enzyme XapI optimiz es the diagnosis of facioscapulohumeral muscular dystrophy by uniquely dige sting 4-derived repeat units and leaving 10-derived repeat units undigested , thus complementing BlnI, which uniquely digests 10-derived repeat units. A triple analysis with EcoRI, EcoRI/BlnI, and XapI unequivocally allows cha racterization of each of the four alleles, whether homogeneous or hybrid. T his is particularly useful in the case of identical sized 4-derived and 10- derived arrays, in situations of suspected facioscapulohumeral muscular dys trophy with nonstandard allele configurations, and for assignment of hybrid fragments to their original alleles.