Purpose of review The recent identification of mutations in five genes coding for proteins with putative or demonstrated glycosyltransferase activity has shed light on a novel mechanism responsible for muscular dystrophy. Abnormal glycosylation of α-dystroglycan appears to be a common finding in all these conditions. Surprisingly, the disease severity due to mutations in several of these genes is extremely variable. This article provides an overview of the clinical, biochemical and genetic advances that have been made over the last year in this field.

Recent findings Mutations in the human LARGE gene, a putative glycosyltransferase mutated in the myodystrophy mouse, have now been identified in a form of human muscular dystrophy. In addition, the clinical variability of patients with mutations in the genes encoding fukutin, protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 and the fukutin-related protein has been significantly expanded. Disease severity in patients with mutations in the gene encoding the fukutin-related protein varies from a severe prenatal form of congenital muscular dystrophy with cobblestone lissencephaly and structural eye defects to a mild form of limb-girdle muscular dystrophy with onset in adult life and neither brain nor eye involvement.

Summary Glycosylation disorders represent a rapidly growing and common group of muscular dystrophies. Accurate genetic diagnosis can now be made for five forms, and it is anticipated that several other variants will eventually fall into these categories.