0000000000820323
AUTHOR
Martin R. Farlow
Spheroid body myopathy revisited
Having reported spheroid body myopathy from Indiana (IN) inherited in an autosomal-dominant fashion several years ago, we now describe additional findings from the Oregon branch—briefly recorded earlier—and confirm earlier studies in another clinically affected IN member of this kinship demonstrating identical spheroid bodies within the myopathic muscle specimens. The spheroid bodies also contained increased amounts of desmin, α-B crystallin, and ubiquitin within muscle fibers. Our studies now have established that spheroid body myopathy is a member of the growing family of desminopathic neuromuscular conditions. © 1997 John Wiley & Sons, Inc. Muscle Nerve20:1127–1136, 1997
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…
A mutation in myotilin causes spheroid body myopathy
Background: Spheroid body myopathy (SBM) is a rare, autosomal dominant, neuromuscular disorder, which has only been previously reported in a single large kindred. Identification of the mutated gene in this disorder may provide insight regarding abnormal neuromuscular function. Methods: The authors completed a detailed clinical evaluation on an extensive kindred diagnosed with SBM. Genome-wide linkage analysis was performed to localize the disease gene to a specific chromosomal region. Further marker genotyping and screening of a positional, functional candidate gene were completed to detect the disease-causing mutation. Pathologic analysis of muscle biopsy was performed on three individuals…