Infantile onset myofibrillar myopathy due to recessive CRYAB mutations.
Mutations in the αB-crystallin (CRYAB) gene, encoding a small heat shock protein with chaperone function, are a rare cause of myofibrillar myopathy with autosomal-dominant inheritance, late-onset and moderate severity. We report a female infant presenting from 4 months with profound muscle stiffness, persistent creatine kinase elevation and electromyography characterized by spontaneous electrical activity and pseudomyotonic discharges. Muscle biopsy suggested a myofibrillar myopathy and genetic testing revealed homozygosity for the CRYAB mutation c.343delT (p.Ser115ProfsX14). These findings suggest a severe, recessively inherited form of CRYAB-related myofibrillar myopathy. Profound muscle stiffness as the main presenting feature indicates αB-crystallin as a potent modifier of muscle contractility.
Department of Paediatric Neurology, Neuromuscular Service, Evelina Children's Hospital, London, UK.
Katharine M L
KM
Forrest
Safa
S
Al-Sarraj
Caroline
C
Sewry
Stefan
S
Buk
S Veronica
SV
Tan
Matthew
M
Pitt
Andrew
A
Durward
Marilyn
M
McDougall
Melita
M
Irving
Michael G
MG
Hanna
Emma
E
Matthews
Anna
A
Sarkozy
Judith
J
Hudson
Rita
R
Barresi
Kate
K
Bushby
Heinz
H
Jungbluth
Elizabeth
E
Wraige
D064211:Connectin; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004576:Electromyography; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007223:Infant; D008840:Microfilament Proteins; D046529:Microscopy, Electron, Transmission; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009210:Myofibrils / Q000473:pathology*; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000503:physiopathology; D038203:alpha-Crystallin B Chain / Q000235:genetics* / Q000378:metabolism
C059215:CRYAB protein, human; D064211:Connectin; D003598:Cytoskeletal Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D038203:alpha-Crystallin B Chain