Nemaline myopathy caused by absence of α‐skeletal muscle actin
KJ Nowak, CA Sewry, C Navarro… - Annals of Neurology …, 2007 - Wiley Online Library
KJ Nowak, CA Sewry, C Navarro, W Squier, C Reina, JR Ricoy, SS Jayawant, AM Childs…
Annals of Neurology: Official Journal of the American Neurological …, 2007•Wiley Online LibraryObjective To investigate seven congenital myopathy patients from six families: one French
Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients
required mechanical ventilation from birth, five died before 22 months, one is ventilator‐
dependent, but one, at 30 months, is sitting with minimal support. All parents were
unaffected. Methods The α‐skeletal muscle actin gene (ACTA1) was sequenced. Available
muscle biopsies were investigated by standard histological and electron microscopic …
Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients
required mechanical ventilation from birth, five died before 22 months, one is ventilator‐
dependent, but one, at 30 months, is sitting with minimal support. All parents were
unaffected. Methods The α‐skeletal muscle actin gene (ACTA1) was sequenced. Available
muscle biopsies were investigated by standard histological and electron microscopic …
Objective
To investigate seven congenital myopathy patients from six families: one French Gypsy, one Spanish Gypsy, four British Pakistanis, and one British Indian. Three patients required mechanical ventilation from birth, five died before 22 months, one is ventilator‐dependent, but one, at 30 months, is sitting with minimal support. All parents were unaffected.
Methods
The α‐skeletal muscle actin gene (ACTA1) was sequenced. Available muscle biopsies were investigated by standard histological and electron microscopic techniques. The expression of various proteins was determined by immunohistochemistry, western blotting, or both.
Results
Three homozygous ACTA1 null mutations were identified: p.Arg41X in the French patient, p.Tyr364fsX in the Spanish patient, and p.Asp181fsX10 in all five British patients. An absence of α‐skeletal muscle actin protein but presence of α‐cardiac actin was shown in all muscle biopsies examined, with more α‐cardiac actin in the biopsy from the child with the greatest muscle function. Muscle biopsies from all patients exhibited nemaline bodies whereas three also contained zebra bodies.
Interpretation
The seven patients have recessive nemaline myopathy caused by absence of α‐skeletal muscle actin. The level of retention of α‐cardiac actin, the skeletal muscle fetal actin isoform, may determine α‐skeletal muscle actin disease severity. This has implications for possible future therapy. Ann Neurol 2006
Wiley Online Library