No abstract

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children) new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Sub-classification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM”, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM”. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy) rules out IIM, leaving a probability of ≥50 to <55% as “possible IIM”. Conclusions The EULAR/ACR classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite”, “probable”, and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.