Congenital muscular dystrophy with primary laminin alpha2 (merosin) deficiency presenting as inflammatory myopathy.
Ten laminin alpha2-deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin alpha2-deficient patients were carrying a diagnosis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin-deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10-kb laminin alpha2-coding sequence was screened for causative mutations by reverse transcriptase-polymerase chain reaction/single-stranded conformational polymorphism analysis in muscle biopsy specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss-of-function deletion mutations were identified in both alleles of 1 patient. Muscle histopathology in this patient showed a striking inflammatory infiltrate of T cells and B cells. Reexamination of biopsy specimens from other laminin alpha2-deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subset of congenital muscular dystrophy is proposed. Our data show that muscle histopathology showing a neonatal inflammatory process should be considered consistent with congenital muscular dystrophy.
Pegoraro
E
E
Department of Molecular Genetics, University of Pittsburgh, School of Medicine, PA 15261, USA.
Mancias
P
P
Swerdlow
S H
SH
Raikow
R B
RB
Garcia
C
C
Marks
H
H
Crawford
T
T
Carver
V
V
Di Cianno
B
B
Hoffman
E P
EP
D001483:Base Sequence; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D015252:Deoxyribonucleases, Type II Site-Specific; D004576:Electromyography; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D007797:Laminin / Q000172:deficiency* / Q000235:genetics; D008875:Middle Aged; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology*; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D017285:Polymyositis / Q000503:physiopathology*; D017384:Sequence Deletion
D007797:Laminin; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases