In Victoria, Australia, Sillence et al. (1979) found type III OI to be about one-eighth as frequent as dominantly inherited OI with blue sclerae. Scleral hue, which may be bluish at birth, usually normalizes with age. Patients reported ... In Victoria, Australia, Sillence et al. (1979) found type III OI to be about one-eighth as frequent as dominantly inherited OI with blue sclerae. Scleral hue, which may be bluish at birth, usually normalizes with age. Patients reported in the literature with normal sclerae have shown progressive deformity of the limbs in childhood and of the spine in late childhood and adolescence. Dentinogenesis imperfecta is particularly striking, especially in the primary dentition. Sillence et al. (1979) observed 2 families with consanguineous parents. Some of the cases referenced in 166210 presumably represent this type. Peltonen et al. (1980) studied procollagen synthesis by fibroblasts from a male patient who died at age 18 years after a fall from his wheelchair. He was born with multiple fractures. He had blue sclerae, but normal dentition. He developed severe kyphoscoliosis and multiple limb deformities. Whether this represented Sillence's type III OI or new mutation for Sillence's type I OI (166200) was not clear. When fibroblasts were incubated with tritiated-mannose, type I procollagen contained 2 to 3 times more labeled-mannose than that from normal fibroblasts, although type III procollagen produced simultaneously by the patient's fibroblasts was not abnormal. The type I collagen synthesized by the patient's fibroblasts was secreted into the medium abnormally slowly. The patient's procollagen formed insoluble aggregates with abnormal facility. The findings were interpreted as indicating an amino acid change, presumably in the COOH-terminal propeptide because this was the site of the mannose, which altered the protein's glycosylation. Unfortunately, it was not possible to study the collagen of the parents of this case; this might have permitted conclusions as to whether the patient was homozygous for an amino acid substitution or heterozygous. Nicholls et al. (1979, 1984) described absence of alpha-2 chains in a child of a third-cousin marriage who they suggested had Sillence type III OI, although the sclerae were described as 'significantly blue.' Type I collagen consisted only of alpha-1 chains, i.e., was an alpha-1 trimer. The child had remarkably mild manifestations. The first recognized fracture, of the humerus, occurred at age 5 weeks. Following another break 2 weeks later, x-rays showed normal width of bones with signs of several earlier fractures. Nicholls et al. (1984) concluded that the child was homozygous for an abnormal pro-alpha-2(I) chain (120160) which does not associate with pro-alpha-1(I) chains and therefore is not incorporated into triple helical trimers of type I procollagen. In a child with type III OI, Pope et al. (1985) showed an abnormality of the alpha-2 chain of type I collagen, specifically a 4-bp deletion which led to frame shift at the carboxyl end of the protein. Because of this, the normal type I helix could not be assembled and the alpha-2 gene product was degraded intracellularly. Tenni et al. (1988) reported a male infant with type III OI in whom biochemical analysis of the alpha-1(I) chains was consistent with a mutation towards the C-terminus of the triple helix or within the C-propeptide. Byers et al. (2006) published practice guidelines for the genetic evaluation of suspected OI.
Faqeih et al. (2009) reported 3 unrelated patients with OI type III, brachydactyly, and intracranial hemorrhage, 1 of whom was previously described by Cole and Lam (1996), who all had glycine mutations involving exon 49, in the most ... Faqeih et al. (2009) reported 3 unrelated patients with OI type III, brachydactyly, and intracranial hemorrhage, 1 of whom was previously described by Cole and Lam (1996), who all had glycine mutations involving exon 49, in the most C-terminal part of the triple helical domain of COL1A2 (120160.0037, 120160.0054, and 120160.0055, respectively). Faqeih et al. (2009) suggested that mutations in this region of COL1A2 carry a high risk of abnormal limb development and intracranial bleeding.
Starman et al. (1989) reported a family in which the OI III phenotype was caused by a dominant mutation in the COL1A1 gene that resulted in substitution of cysteine for glycine at position 526 of the triple helix ... Starman et al. (1989) reported a family in which the OI III phenotype was caused by a dominant mutation in the COL1A1 gene that resulted in substitution of cysteine for glycine at position 526 of the triple helix (120150.0005). This and other experience suggested to Starman et al. (1989) that a significant proportion of individuals with the OI III phenotype have a dominant mutation which, in some families, is inherited. Pruchno et al. (1991) found a heterozygous de novo mutation, gly154-to-arg, in 2 unrelated individuals with a progressive deforming variety of OI compatible with OI type III (see 120150.0030). Dominant inheritance of OI III was also supported by Cohen-Solal et al. (1991), who found biochemical evidence of heterozygosity. The parents were nonconsanguineous. Parental gonadal mosaicism was presumed. Molyneux et al. (1993) also presented molecular evidence of heterozygosity for a new dominant mutation in a child with progressive deforming OI. They concluded with the statement that 'in the majority of instances, the phenotype results from heterozygosity for mutations in one of the genes that encode chains of type I collagen.' De Paepe et al. (1997) identified homozygosity for a gly751-to-ser mutation of the COL1A2 gene (120160.0039) in 2 sibs; the 2 parents, who were first cousins, and 2 other sibs were heterozygous and had manifestations consistent with type I OI (166200). Cabral et al. (2001) reported a 13-year-old girl with severe type III OI in whom they identified heterozygosity for a gly76-to-glu substitution in the COL1A1 gene (120150.0065). The authors stated that this was the first delineation of a glutamic acid substitution in the alpha-1(I) chain causing nonlethal osteogenesis imperfecta. Autosomal dominant inheritance of OI type III is represented by a family in which the affected member of the first generation had molecularly proven mosaicism for a heterozygous 562-bp deletion in the COL1A1 gene (120150.0054) (Cabral and Marini, 2004).
Beighton and Versfeld (1985) suggested that type III OI is relatively high in the black population of South Africa. The high frequency did not seem to be limited to one tribe. Whereas in Australian whites the ratio of ... Beighton and Versfeld (1985) suggested that type III OI is relatively high in the black population of South Africa. The high frequency did not seem to be limited to one tribe. Whereas in Australian whites the ratio of OI I to OI III is about 7 to 1 (Sillence et al., 1979), in South African blacks it is about 1 to 6. The authors cited a report of a relatively high frequency of OI III in Nigeria. In Zimbabwe, Viljoen and Beighton (1987) identified 58 cases of OI in institutions for crippled persons; 42 of the patients had the rare OI type III. The Shona and the Ndebele, both major tribal groups, had a similar and relatively high gene frequency for this disorder. Both tribes were derived from common progenitors, but until 150 years earlier had been geographically separated for 2 millennia; they remain culturally and socially distinct. Viljoen and Beighton (1987) inferred that the mutation for OI III in Africa occurred at least 2000 years ago.