Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy.

X-linked recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoprotein. The dystrophin-glycoprotein complex has been proposed to span the sarcolemma to provide a link between the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated protein. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive muscular dystrophy (SCARMD) with a DMD-like phenotype. Here we report the specific deficiency of the 50K dystrophin-associated glycoprotein (M(r) 50,000) in sarcolemma of SCARMD patients. Therefore, the loss of this glycoprotein is a common denominator of the pathological process leading to muscle cell necrosis in two forms of muscular dystrophy, DMD and SCARMD.     

Genetic and autoradiographic studies of tritiated thymidine in testes ofDrosophila melanogaster

Zusammenfassung Die Aufnahme von H³-Thymidin in 16 h alte männliche Larven vonDrosophila melanogaster wurde autoradiographisch verfolgt und die mutagene Wirkung des einverleibten H³-Thymidin durch die Bestimmung der Häufigkeit der geschlechtsgebundenen rezessiven Mutationen gemessen. Es zeigte sich, dass das der männlichen Larve derDrosophila melanogaster verabreichte H³-Thymidin eine bedeutende Häufigkeit der Mutationen verursacht.

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Supported in part by Grant G-6097 of the National Science Foundation.     

Effects of tetraphenyboron on erythrocyte enzymes

Rusemen El tratamiento de glóbulos rojos humanos con concentraciones no-hemolíticas de borotetrafenilo causa una reducción irreversible en las activides de la glucosa-6-fosfato dehidrogenasa, una enzima citoplasmática y de la acetilcolinesterasa, ubicada en la superficie externa de la membrana eritrocitaria. El tratamiento casi no tiene efecto alguno sobre la fosfatasa ácida.     

A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G --> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.     

Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals that features progressive loss in visual acuity leading, in many cases, to legal blindness. Phenotypic variations and loss of retinal ganglion cells, as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment. The OPA1 gene has been localized to 3q28-q29 (refs 13-19). We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology.     

Alterations of the erythrocyte membrane caused by fluorinated dinitrobenzenes

Zusammenfassung Inaktivierung der Acetylcholinesterase in der Erythrozytenmembran mit 1-Fluor-2,4-dinitrobenzol und 1,5-Difluor-2,4-dinitrobenzol konnte durch blutgruppenspezifische Antikörper nicht beeinflusst werden. Nach Difluordinitrobenzol-Behandlung zeigten die Blutkörperchen Verlust der Agglutinabilität und die Membranen eine Herabsetzung ihrer Absorptionsfähigkeit für homologe Antikörper.

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This work was supported by research grant No. HD 01461 from the National Institutes of Health, U.S.P.H.S.