Molecular diagnosis and counseling in a family presenting compound heterozygosity for autosomal recessive limb-girdle muscular dystrophy

Molecular diagnosis and conseling in a family presenting compound heterozyg osity for autosomal recessive limb-gridle muscular dystrophy,. The present report concerns two patients, male and female siblings, manifesting a diffe rent degree of severity for the same autosomal recessive limb-girdle muscul ar dystrophy. The index case (male sib) carried the clinical diagnosis of B ecker muscular dystrophy at the time when the sister, with a much milder pr esentation, first sought counseling and prenatal diagnosis for a pregnancy already in course. Molecular and immunocytochemical tests then available fa voured the diagnosis of an autosomal recessive myopathy, but did not enable exclusion of a dystrophinopathy. The couple was counseled accordingly, alt hough prenatal diagnosis could not be offered. Both patients were later fou nd to carry one gamma and two alpha -sarcoglycan gene mutations, one of the latter being new. This raised a counseling dilemma: depending on which com bination was the disease-causing genotype, there would be a minimal or a si gnificant 25% risk to offspring. We describe the studies carried out and em phasise the importance of differential diagnosis and extensive molecular ch aracterisation in this group of disorders, so as to enable correct genetic counseling and prenatal diagnosis.