The inheritance of progressive muscular dystrophy in Japan

Summary In conclusion, there were no apparent differences between Japanese and foreign cases in clinical types, the frequency of each type, sex ratio, the age of onset, modes of the inheritance etc., except for a peculiar type of the disorder found in the South-Western Islands. However, sporadic cases were seem to be comparatively often encountered in each type especially in the Duchenne and limb-girdle type. Further, large families with as many victims as in foreign cases have not yet been reported in Japan.Professor of Nagoya University, M. D., D. Med. Sc.     

Serum creatine kinase isoenzymes in progressive muscular dystrophy

Creatine kinase isoenzymes in sera and muscle biopsies obtained from 50 controls, 72 patients with progressive muscular dystrophy (PMD), 68 patients with other neuromuscular disorders, 17 carriers of Duchenne-type PMD and 15 patients with myocardial infarction were studied. MB isoenzyme was detected in the sera of 58 patients with PMD and 56 out of 61 muscle biopsies. The MB activity varied between 4 and 400 IU/1 or 3.4--22% of total activity. The MB activity was demonstrated in a considerably smaller number of cases with polymyositis, dystrophic myotonia and Kugelberg-Welander disease. The MB isoenzyme in sera of PMD persisted for many years. It is admitted that the MB isoenzyme in the serum of patients with PMD originates chiefly from skeletal muscle.     

Merosin-deficient congenital muscular dystrophy: neuropathology case reports

The aims of our study were: to present cases of congenital muscular dystrophy (CMD) with deficiency in merosin and the importance of immunohistochemistry in the diagnosis of merosin-deficient CMD. In four years (1997-2000), we found three patients with merosin-deficient CMD, one of them having an unusual clinical and pathological manifestation of the disease. Muscle biopsies of gastrocnemius or quadriceps muscles were investigated. In addition with the conventional HE staining, indirect immunohistochemistry for merosin, dystrophin, utrophin and for the proteins of the dystrophin associated complex (α,β, γ- sarcoglycans; β-dystroglycan) was performed on cryosections. The findings suggest that there is no correlation between the clinical and histological picture of the disease and the expression of merosin in skeletal muscles. The degree of muscle involvment (assessed by histology) is parallel with the clinical neuromotor deficiency, but not with expression of merosin, which can be absent even in mild cases. The clinical investigations as well as current morphological techniques, only together with immunohistochemistry can differentiate between merosin - deficient CMD and other muscular dystrophy forms.     

Genetics and epigenetics of facio-scapulohumeral progressive (Landouzy-Dejerine) muscular dystrophy

Landouzy-Dejerine muscular dystrophy is a rare hereditary disease with prevalence of 0.9 to 1.4 in 100,000. Clinically the disease is characterized by weakness and atrophy of the facial and shoulder girdle muscles. It is caused by partial deletion of the 3.3-kb subtelomeric D4Z4 repeat on chromosome 4 (locus 4q35). This paper presents a critical review of the literature data and hypotheses explaining molecular mechanisms of progressive fascioscapulohumeral muscular dystrophy.     

Serum activity of C1 inactivator in Duchenne-type progressive muscular dystrophy

We previously found that the level of the immunoreactive activity of C1 inactivator in the plasma Duchenne-type patients with progressive muscular dystrophy was lower than that in normal boys. Therefore, we investigated the level of the C1 inactivator inhibiting activity against C1 esterase in the serum from PMD patients. The mean level of anti-esterase activity of C1 inactivator against C1 esterase in the serum from PMD was 50% lower than that of the control group (P less than 0.05).     

A linkage study of Emery-Dreifuss muscular dystrophy

Summary We have searched for linkage between polymorphic loci defined by DNA markers on the X chromosome and X-linked Emery-Dreifuss muscular dystrophy (EDMD). There are high recombination rates between EDMD and the Xp loci known to be linked to Becker and Duchenne muscular dystrophy. There is a suggestion of linkage between EDMD and the loci DXS52 and DXS15, defined by probes St 14 and DX13 respectively, located at Xq28. for DXS15=1.14 at =0.15. This is in agreement with the previously reported linkage between a disorder strongly resembling EDMD and colour-blindness (Thomas et al. 1972), suggesting that there is a second locus on the X chromosome concerned with muscle integrity.     

Oculopharyngeal muscular dystrophy: a late-onset polyalanine disease

Oculopharyngeal muscular dystrophy (OPMD) is a muscle disease of late onset associated with progressive ptosis of the eyelids, dysphagia, and unique tubulofilamentous intranuclear inclusions (INIs). OPMD is usually transmitted as an autosomal dominant trait (OMIM 164300). A rarer allelic autosomal recessive form has also been observed (OMIM 257950). Both forms are caused by short (GCG)8-13 expansions in the polyadenylate-binding protein nuclear 1 gene (PABPN1) located on chromosome 14q11.1. The mutations cause the lengthening of an N-terminal polyalanine domain. Both slippage and unequal recombination have been proposed as the mutation mechanisms. The size of the mutation has not yet been conclusively shown to inversely correlate with the severity of the phenotype. Mutated PABPN1 proteins have been shown to be constituents of the INIs. The INIs also contain ubiquitin, proteasome subunits, HSP 40, HSP 70, SKIP, and abundant poly(A)-mRNA. The exact mechanism responsible for polyalanine toxicity in OPMD is unknown. Various intranuclear inclusion dependent and independent mechanisms have been proposed based on the major known function of PABPN1 in polyadenylation of mRNA and its shuttling from the nucleus to the cytoplasm. OPMD is one of the few triplet-repeat diseases for which the function of the mutated gene is known. Because of the increasing number of diseases caused by polyalanine expansions and the pathological overlap with CAG/polyglutamine diseases, what pathological insight is gained by the study of OPMD could lead to a better understanding of a much larger group of developmental and degenerative diseases.     

Further observations by electron microscope of striated muscle in progressive Duchenne muscular dystrophy

Gastrocnemius muscle fragments of children affected by clinically diagnosed progressive muscular dystrophy of Duchenne have been studied. At the light microscope, in the semi-thin sections, the more evident changes are represented by a wide diameter range of the fibers and fatty infiltration. Some fibers show numerous nuclei in their central part, a sarcoplasmic degeneration of vacuolar type and an irregular and tortuous course of the myofibrils. Moreover, the ultrastructural findings have shown characteristic changes in myofilaments and Z bands represented by: streaming of the Z bands, collection of the triads and concentric laminated bodies. These observations have pointed out a certain gradualness of the alterations, starting from focal changes of Z band to the complete disarrangement of myofilaments.