Muscular dystrophy associated with β‐dystroglycan deficiency

Abstract

beta-Dystroglycan, a 43-kd transmembrane dystrophin-associated glycoprotein, plays an important role in linking dystrophin to the laminin-binding alpha-dystroglycan. alpha-/beta-Dystroglycan is encoded by a single gene on chromosome 3p21 and ubiquitously expressed in muscle and nonmuscle tissues. No known human diseases have been mapped to this locus. Here, we describe the selective deficiency of beta-dystroglycan in a 4-year-old Saudi boy with muscular dystrophy. The patient had a borderline elevation of serum creatine kinase level and early-onset proximal symmetrical muscle weakness and wasting without calf hypertrophy. The milder phenotype may suggest a secondary deficiency of beta-dystroglycan; however, the unique immunofluorescence labeling suggests that the patient may present a novel form of muscular dystrophy.

Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ‐deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency

“…4 B, C ). These types of defects usually lead to dystroglycanopathy in human or mouse models like DG‐null animals, with a clear dystrophic phenotype (54, 55). In particular, signs of necrosis, a switch from fast‐ to slow‐fiber types, fibrosis, regeneration events, inflammation, and increased mitochondrial metabolism are generally detected in muscles.…”

Form and function: The laminin family of heterotrimers

“…The second major receptor for α2‐laminins in the muscle sarcolemma is α‐dystroglycan (Ervasti and Campbell, 1993; Henry and Campbell, 1996; Higuchi et al, 1994; Ibraghimov‐Beskrovnaya et al, 1993; Klietsch et al, 1993; Salih et al, 1996). α‐dystroglycan is a dumbbell‐shaped molecule rich in mucinous sialoglycoconjugate in its neck region that can bind to laminins 1–4, agrin, and perlecan (Brancaccio et al, 1995; Smalheiser and Kim, 1995; Talts et al, 1999).…”

A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of α-dystroglycan

“…To date, no disease has been found that is due to primary mutations in dystroglycan, although a mild form of muscular dystrophy associated with a secondary b-dystroglycan deficiency has been described [23]. In addition to LGMD2I, abnormal a-dystroglycan expression has been documented in several forms of congenital muscular dystrophy (CMD), with and without central nervous system (CNS) involvement.…”