Gene/Protein
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Symptom
Drug
Enzyme
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Target Concepts:
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Query: UMLS:C0029089 (
ophthalmoplegia
)
3,338
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Muscle contraction upon nerve stimulation relies on excitation-contraction coupling (ECC) to promote the rapid and generalized release of calcium within myofibers. In skeletal muscle, ECC is performed by the direct coupling of a voltage-gated L-type Ca
2+
channel (dihydropyridine receptor; DHPR) located on the T-tubule with a Ca
2+
release channel (ryanodine receptor; RYR1) on the sarcoplasmic reticulum (SR) component of the triad. Here, we characterize a novel class of congenital myopathy at the morphological, molecular, and functional levels. We describe a cohort of 11 patients from 7 families presenting with perinatal hypotonia, severe axial and generalized weakness.
Ophthalmoplegia
is present in four patients. The analysis of muscle biopsies demonstrated a characteristic intermyofibrillar network due to SR dilatation, internal nuclei, and areas of myofibrillar disorganization in some samples. Exome sequencing revealed ten recessive or dominant mutations in
CACNA1S
(Ca
v
1.1), the pore-forming subunit of DHPR in skeletal muscle. Both recessive and dominant mutations correlated with a consistent phenotype, a decrease in protein level, and with a major impairment of Ca
2+
release induced by depolarization in cultured myotubes. While dominant
CACNA1S
mutations were previously linked to malignant hyperthermia susceptibility or hypokalemic periodic paralysis, our findings strengthen the importance of DHPR for perinatal muscle function in human. These data also highlight
CACNA1S
and ECC as therapeutic targets for the development of treatments that may be facilitated by the previous knowledge accumulated on DHPR.
...
PMID:Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy. 2801 42
Dihydropyridine receptor congenital myopathy is a recently described congenital myopathy caused by dominant or recessive mutations in the
CACNA1S
gene. To date, only 11 cases from 7 families were described in a single report. Here, we describe a consanguineous family with three affected children, presenting congenital hypotonia, contractures,
ophthalmoplegia
and respiratory insufficiency, with a novel homozygous mutation in the
CACNA1S
gene. They also showed cognitive delay, pes equinovarus deformity and neurogenic changes that have not been associated with this myopathy in the previous reports. This report expands the phenotypic spectrum of dihydropyridine receptor congenital myopathy and underscores the importance of whole exome sequencing in early onset neuromuscular disorders.
...
PMID:Dihydropyridine Receptor Congenital Myopathy In A Consangineous Turkish Family. 3122 54
