Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia)

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Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses1. Electromyographic investigations reveal repetitive muscle discharges, which may originate from both neurogenic and myogenic alterations2,3. We previously localized the SJS1 locus to chromosome 1p34–p36.1 and found no evidence of genetic heterogeneity4,5. Here we describe mutations, including missense and splicing mutations, of the gene encoding perlecan (HSPG2) in three SJS1 families. In so doing, we have identified the first human mutations in HSPG2, which underscore the importance of perlecan not only in maintaining cartilage integrity but also in regulating muscle excitability.

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Figure 1: Physical and genetic map of the SJS1 locus.
Figure 2: RT–PCR analysis of HSPG2 exon-64 splicing event.
Figure 3: Mutation detection in family SJS1-H.
Figure 4: Predicted topology of perlecan and mutations in SJS1.

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We thank the patients, their families and the physicians for participation; A. Munnich for human chrondrocyte RNA; the UK HGMP for PAC PCR pools of the RPCI-1 library and PAC clones; the Banque de Tissus pour la Recherche de l'Association Française contre les Myopathies (AFM-BTR) for skeletal muscle samples; the cell and DNA banks of the Institut National de la Santé et de la Recherche Médicale (INSERM) U289 and of the Groupe Hospitalier Cochin-Port Royal for lymphoblastoid cell lines and DNA samples; and N. Tabti for comments on the manuscript. S.N. was supported by grants from the Académie Nationale de Médecine and, subsequently, AFM. This work received financial support from AFM and INSERM (APEX).

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Correspondence to Bertrand Fontaine.

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