Usefulness of a CACA repeat polymorphism in genotype assignments in Duchenne/Becker muscular dystrophy

Abstract

RFLP analysis in Duchenne/Becker muscular dystrophy (D/BMD) has been limited by the lack of informative marker loci at the 3' end of the dystrophin gene. Recently a CACA repeat polymorphism was described in the 3' untranslated end of the dystrophin gene which we have found helpful in genotype assignments of D/BMD families when an RFLP approach is required. The CACA repeat marker has 2 common alleles (1 and 2) that are easily visualized by a nonradioactive PCR method followed by polyacrylamide gel electrophoresis. We present 2 families which demonstrate the use of this polymorphism. Since 35-50% of females are heterozygous, this locus is a useful marker in RFLP analysis of D/BMD families.

Molecular diagnosis of dystrophinopathies using a multi‐technique analysis algorithm

“…Several intronic short tandem‐repeat [STR‐(CA)n] polymorphisms have been identified within the dystrophin gene, and many are located in deletion/recombination hot‐spot regions . We used a set of 8 highly polymorphic STR markers to perform a segregation analysis in these families.…”

“…Several intronic short tandem-repeat [STR-(CA)n] polymorphisms have been identified within the dystrophin gene, and many are located in deletion/recombination hot-spot regions. 12,[23][24][25][26][27] We used a set of 8 highly polymorphic STR markers to perform a segregation analysis in these families. The amplified microsatellites were labeled using a specific 32 Pprimer [STRs: introns 1 (DYSII), 7, 25, 44, 45, and 63], or a specific 6-FAM-primer [STR: introns 1 (DYSII), 62, and 67].…”

Direct Deletion Analysis in Two Duchenne Muscular Dystrophy Symptomatic Females Using Polymorphic Dinucleotide (CA)n Loci within the Dystrophin Gene

“…However, the ascertainment of female carriers by these techniques is often difficult because of the presence of the normal X chromosome that masks the pathogenic deletion in its mutant counterpart. Short tandem-repeat (STR) (CA) n polymorphisms have been identified in different regions of the dystrophin gene (Beggs and Kunkel, 1990;Oudet et al, 1990;Feener et al, 1991;Miller et al, 1992;King et al, 1994); several of them are located in deletion-prone regions (Clemens et al, 1991). We used a set of seven highly polymorphic STR markers within the human dystrophin gene to perform a segregation analysis in 2 symptomatic females and their relatives in order to search for the hemizygous patterns that reveal the presence of a mutated DMD gene.…”