Abnormal expression of laminin suggests disturbance of sarcolemma-extracellular matrix interaction in Japanese patients with autosomal recessive muscular dystrophy deficient in adhalin.

Abstract

Dystrophin is associated with several novel sarcolemmal proteins, including a laminin-binding extracellular glycoprotein of 156 kD (a-dystroglycan) and a transmembrane glycoprotein of 50 kD (adhalin). Deficiency of adhalin characterizes a severe autosomal recessive muscular dystrophy prevalent in Arabs. Here we report for the first time two mongoloid (Japanese) patients with autosomal recessive muscular dystrophy deficient in adhalin. Interestingly, adhalin was not completely absent and was faintly detectable in a patchy distribution along the sarcolemma in our patients. Although the M and B2 subunits of laminin were preserved, the B1 subunit was greatly reduced in the basal lamina surrounding muscle fibers. Our results raise a possibility that the deficiency of adhalin may be associated with the disturbance of sarcolemma-extracellular matrix interaction leading to sarcolemmal instability. (J. Clin. Invest. 1994. 94:601-606.)

Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency.

“…The resulting amino acid substitutions are expected to reduce the hydrophilicity of the protein, and furthermore the substitution of Arg by Cys with a sulfhydryl radical (-SH) and the insertion of five amino acids would probably affect the secondary and tertiary structures of adhalin. These could disturb its interaction with other membrane-associated proteins or the components of the basal lamina (16,(26)(27)(28)(29)(30). It is also conceivable that alteration of the higher order structure of mutant adhalin may cause its rapid degeneration.…”

“…Deficiency of adhalin (a 50-kD dystrophin-associated glycoprotein) in the skeletal muscle has been found in several families with SCARMD (12)(13)(14)(15)(16). Recently, complete absence of adhalin in skeletal muscle and missense mutations in the adhalin gene were identified in a single French family with autosomal recessive muscular dystrophy which was less clinically severe than SCARMD (17).…”

Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy.

“…4, C and D). Since both proliferative myoblasts and differentiated myotubes express the ␣7B integrin subunit (37-41), the apparent increased sarcolemmal expression of this subunit may be the result of enhanced myoblast fusion with actively regenerating dystrophic myofibers (11)(12)(13)(14)(15)(16)(17). Thus, these data indicate that the loss and/or disruption of ␣7␤1D integrin isoforms in striated muscle is correlated specifically to merosin deficiency, and is not an overall consequence of muscular dystrophy.…”

“…Mutations in the gene for the ␣ 2 chain ( LAMA2 ) of merosin, which lead to either a loss of expression or to the expression of a defective molecule, have been shown to cause a severe form of autosomal recessive congenital muscular dystrophy (CMD) termed merosin-deficient CMD (MCMD; 2, 4, 8, 10). A reduction in merosin ␣ 2 and/or ␤ 1/ ␤ 2 chains has been observed in other muscular dystrophies, such as the Fukuyama congenital muscular dystrophy (FCMD), the Finnish muscle-eye-brain disease (MEB), and the Walker-Warburg syndrome (4,(11)(12)(13)(14). However, the genetic defects responsible for these other diseases have yet to be identified.…”

Statistically Significant Differences in the Number of CD24 Positive Muscle Fibers and Satellite Cells between Sarcoglycanopathy and Age-Matched Becker Muscular Dystrophy Patients.

“…The physiological role of each sarcoglycan protein and the pathophysiology of sarcoglycanopathy are poorly understood. Wehave reported that there is reduction of the beta-1 subunit of laminin, heparan sulfate proteoglycan (HSPG), and HCAM in*Japanese patients with sarcoglycanopathy (6)(7)(8). The expression of the CD24molecule, a glycoprotein expressed on the surface of most B lymphocytes and differentiating neuroblasts, was reported to be associated with a subpopulation of regenerative fibers in diseased muscles (9).…”