S. Nicole et al., Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia), NAT GENET, 26(4), 2000, pp. 480-483
Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder char
acterized by permanent myotonia (prolonged failure of muscle relaxation) an
d skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing
of the diaphyses and irregular epiphyses(1). Electromyographic investigatio
ns reveal repetitive muscle discharges, which may originate from both neuro
genic and myogenic alterations(2,3). We previously localized the SJS1 locus
to chromosome 1p34-p36.1 and found no evidence of genetic heterogeneity(4,
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 als
o in regulating muscle excitability.