The chondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth or development of cartilage. Current classification is based on mode of inheritance as well as clinical, histologic, and/or radiographic features. A clinical spectrum of chondrodysplasia phenotypes, ranging from mild to perinatal lethal, is due to defects in the gene for type II collagen, COL2A1. This spectrum includes Stickler syndrome, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), achondrogenesis type II, and hypochondrogenesis. Individuals affected with these disorders exhibit abnormalities of the growth plate, nucleus pulposus, and vitreous humor, which are tissues that contain type II collagen. The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which are not seen in SEDC). The phenotype was first described by Murdoch and Walker in 1969, and a series of 14 patients was later reported by Anderson et al. The observation of two affected sibs born to unaffected parents led to the classification of SEMD Strudwick as an autosomal recessive disorder. We now describe the biochemical characterization of defects in alpha 1(II) collagen in three unrelated individuals with SEMD Strudwick, each of which is due to heterozygosity for a unique mutation in COL2A1. Our data support the hypothesis that some cases, if not all cases, of this distinctive chondrodysplasia result from dominant mutations in COL2A1, thus expanding the clinical spectrum of phenotypes associated with this gene.
"The same mutation, the G504S, was observed associated with a mild phenotype in a 24-year-old patient and also in a patient aged 60 years described as having the diagnosis of spondyloepiphyseal dysplasia tarda, autosomal dominant (OMIM #184100) [Nishimura et al., 2005]. In addition, a similar mutation in the same position, the G504C, was reported in a patient with the phenotype of SED associated with major metaphyseal involvement, also recognized as SED Strudwick type [Tiller et al., 1995]. Likewise, while the G513S was seen in a female child 4 years old with the SEDC-M phenotype [Nishimura et al., 2005]. "
"This mutation clearly interferes with metaphyseal and vertebral ossification to a greater degree than that seen in SEMD-S. Mutations previously reported in SEMD-S are shown in figure 4 [Tiller et al., 1995; Kaitila et al., 1996; Tysoe et al., 2003; Walter et al., 2007]. Patients with the Gly283Arg or V783del mutations have limb asymmetry, but vertebral involvement was mild in these cases. "
[Show abstract][Hide abstract] ABSTRACT: Dysspondyloenchondromatosis (DSC) is a rare skeletal dysplasia that has currently been classified into the group of spondylometaphyseal dysplasias. To date, only 12 affected individuals have been reported. All cases are sporadic, and the etiology remains unknown. Distinctive features of DSC are anisospondyly and enchondroma-like lesions in the metaphyseal and diaphyseal portions of the long tubular bones. Affected individuals usually develop kyphoscoliosis and asymmetric limb shortening at an early age. Interestingly, some of the skeletal changes overlap with spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, a rare type II collagen disorder. Based on this resemblance we postulated that DSC may be allelic to SEMD Strudwick type and therefore performed a COL2A1 analysis in an affected boy who was diagnosed as having DSC at the age of 3 years. The identification of a novel heterozygous COL2A1 missense mutation (p.Gly753Asp) in the proband confirms our hypothesis and suggests that DSC may be another type II collagen disorder.
"plates, they did not yield the basic defect in achondroplasia . In fact, in comparison to similar studies on the spondyloepiphyseal dysplasia family of human chondrodysplasias, in which such studies had been very informative [Lee et al., 1989; Murray et al., 1989; Tiller et al., 1995], these studies were not very revealing. "
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