Clinical heterogeneity of adhalin deficiency.
We report adhalin deficiency in 8 patients with clinically diagnosed muscular dystrophy, dystrophic histopathological features, high plasma creatine kinase levels, normal expression of dystrophin, and marked variability of symptoms. Although the distribution of hyposthenia was similar in all 8 patients and predominantly involved muscles in the pelvic girdle, age at onset and rate of disease progression were highly variable: In 2 patients onset, at ages 24 and 25, was later than has been previously observed. We found no apparent relation between disease severity and the quantity of adhalin expressed. Two kinds of myopathy with adhalin deficiency have been reported: one caused by a mutation in the adhalin gene on chromosome 17 (primary adhalinopathy) and the other linked to chromosome 13. The product of the gene on chromosome 13 is probably associated with adhalin and its deficiency results in secondary adhalinopathy. The severity of clinical phenotypes in these adhalinopathies seems to relate more to the kind and site of the mutations than to the residual amount of the protein. We also detected a variable reduction in the laminin beta 1 subunit by immunohistochemistry in most patients, confirming that this is commonly associated with adhalin deficiency.
Morandi
L
L
Department of Neuromuscular Diseases, Istituto Nazionale Neurologico C. Besta, Milano, Italy.
Barresi
R
R
Di Blasi
C
C
Jung
D
D
Sunada
Y
Y
Confalonieri
V
V
Dworzak
F
F
Mantegazza
R
R
Antozzi
C
C
Jarre
L
L
Pini
A
A
Gobbi
G
G
Bianchi
C
C
Cornelio
F
F
Campbell
K P
KP
Mora
M
M
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000378:metabolism*; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D007797:Laminin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans