Abstract | IMPORTANCE: OBJECTIVE: DESIGN, SETTING, AND PARTICIPANTS: Clinical data including medical and family histories were collected at research laboratories at Boston Children's Hospital and Jules Stein Eye Institute (Engle and Demer labs) for affected and unaffected family members from 2 pedigrees in which patients presented with total ophthalmoplegia, facial weakness, and myopathy. INTERVENTION: Homozygosity mapping and whole-exome sequencing were conducted to identify causative mutations in affected family members. Histories, physical examinations, and clinical data were reviewed. MAIN OUTCOME AND MEASURE: RESULTS: Missense mutations resulting in 2 homozygous RYR1 amino acid substitutions (E989G and R3772W) and 2 compound heterozygous RYR1 substitutions (H283R and R3772W) were identified in a consanguineous and a nonconsanguineous pedigree, respectively. Orbital magnetic resonance imaging revealed marked hypoplasia of extraocular muscles and intraorbital cranial nerves. Skeletal muscle biopsy specimens revealed nonspecific myopathic changes. Clinically, the patients' ophthalmoplegia and facial weakness were far more significant than their hypotonia and limb weakness and were accompanied by an unrecognized susceptibility to malignant hyperthermia. CONCLUSIONS AND RELEVANCE:
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Authors | Sherin Shaaban, Leigh Ramos-Platt, Floyd H Gilles, Wai-Man Chan, Caroline Andrews, Umberto De Girolami, Joseph Demer, Elizabeth C Engle |
Journal | JAMA ophthalmology
(JAMA Ophthalmol)
Vol. 131
Issue 12
Pg. 1532-40
(Dec 2013)
ISSN: 2168-6173 [Electronic] United States |
PMID | 24091937
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ryanodine Receptor Calcium Release Channel
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Topics |
- Amino Acid Substitution
- Blepharoptosis
(diagnosis, genetics)
- Child
- Consanguinity
- DNA Mutational Analysis
- Diseases in Twins
(genetics)
- Exome
(genetics)
- Eye Diseases, Hereditary
(diagnosis, genetics)
- Female
- Fibrosis
- Genotype
- Homozygote
- Humans
- Infant
- Magnetic Resonance Imaging
- Male
- Malignant Hyperthermia
(diagnosis, genetics)
- Mobius Syndrome
(diagnosis, genetics)
- Mutation, Missense
- Ophthalmoplegia
- Pedigree
- Ryanodine Receptor Calcium Release Channel
(genetics)
- Twins, Dizygotic
(genetics)
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