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Autosomal dominant eccentric core disease caused by a heterozygous mutation in the MYH7 gene
- Source :
- Journal of Neurology, Neurosurgery, and Psychiatry
- Publication Year :
- 2014
-
Abstract
- Background Autosomal dominant (AD) central core disease (CCD) is a congenital myopathy characterised by the presence of cores in the muscle fibres which correspond to broad areas of myofibrils disorganisation, Z-line streaming and lack of mitochondria. Heterozygous mutations in the RYR1 gene were observed in the large majority of AD-CCD families; however, this gene was excluded in some of AD-CCD families. Objective To enlarge the genetic spectrum of AD-CCD demonstrating mutations in an additional gene. Patients and methods Four affected AD family members over three generations, three of whom were alive and participate in the study: the mother and two of three siblings. The symptoms began during the early childhood with mild delayed motor development. Later they developed mainly tibialis anterior weakness, hypertrophy of calves and significant weakness (amyotrophic) of quadriceps. No cardiac or ocular involvement was noted. Results The muscle biopsies sections showed a particular pattern: eccentric cores in type 1 fibres, associated with type 1 predominance. Most cores have abrupt borders. Electron microscopy confirmed the presence of both unstructured and structured cores. Exome sequencing analysis identified a novel heterozygous missense mutation p.Leu1723Pro in MYH7 segregating with the disease and affecting a conserved residue in the myosin tail domain. Conclusions We describe MYH7 as an additional causative gene for AD-CCD. These findings have important implications for diagnosis and future investigations of AD-congenital myopathies with cores, without cardiomyopathy, but presenting a particular involvement of distal and quadriceps muscles.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
Heterozygote
Neuromuscular disease
Mutation, Missense
Biology
MYOPATHY
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
Myopathy, Central Core
Myopathy
Exome sequencing
Aged
RYR1
Genetics
Myosin Heavy Chains
medicine.disease
NEUROPATHOLOGY, MUSCLE
Congenital myopathy
Pedigree
Radiography
Psychiatry and Mental health
Muscle Fibers, Slow-Twitch
Neuromuscular
Surgery
MYH7
Female
Neurology (clinical)
MUSCLE DISEASE
medicine.symptom
Cardiac Myosins
Central core disease
Subjects
Details
- ISSN :
- 1468330X
- Volume :
- 85
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of neurology, neurosurgery, and psychiatry
- Accession number :
- edsair.doi.dedup.....8bd4f3799c0a20e987bb18a58c002aad