GENETIC-COUNSELING OF ISOLATED CARRIERS OF DUCHENNE MUSCULAR-DYSTROPHY

It has recently become possible to detect female carriers of Duchenne muscular dystrophy with no affected male relative in the family. These ''isolated carriers'' represent about 10% of women with high serum cr eatine phosphokinase (CPK) levels and clinical evidence of a muscle di sease. Most isolated carriers ascertained by clinical and/or CPK level s and diagnosed by dystrophin immunostaining of muscle biopsy show sym ptoms of a muscular dystrophy, and often carry the diagnosis of recess ive ''limb-girdle muscular dystrophy'' prior to dystrophin analysis. I t has been difficult to offer genetic counseling and prenatal diagnosi s for Duchenne muscular dystrophy in the families of these isolated ca rriers, largely due to the difficulty in determining which of the dyst rophin alleles segregating in the family harbors the mutation in the h eterozygote. Here we report genetic counseling of three isolated carri ers and their families. In two cases, prenatal diagnosis of at-risk pr egnancies was conducted. We determined X inactivation patterns and inh eritance of X chromosomes in each family, and used this information to define the at-risk dystrophin gene. In all three families, the mutati on was a de novo event, two in the paternal germline, and one in the m aternal germ-line. In each case we show that sibs of the heterozygous woman are at population risk, while pregnancies of each propositus are at high risk. Our results show that accurate genetic counseling and p renatal diagnosis can be offered to these families. (C) 1996 Wiley-Lis s, Inc.