Osteogenesis imperfecta is a connective tissue disorder characterized clinically by bone fragility and increased susceptibility to fractures. Osteogenesis imperfecta type IX is a severe autosomal recessive form of the disorder (summary by van Dijk et al., 2009).
In an inbred Irish Traveller family, Williams et al. (1989) described severe Sillence type II/III (166210/259420) osteogenesis imperfecta in 3 consecutively born children with first-cousin parents. Three other children were unaffected. There had been other infants in the ... In an inbred Irish Traveller family, Williams et al. (1989) described severe Sillence type II/III (166210/259420) osteogenesis imperfecta in 3 consecutively born children with first-cousin parents. Three other children were unaffected. There had been other infants in the kindred with lethal OI. The first sib, a male, died at age 6 weeks. The second, a girl, was living at age 7 years and attended a normal school with the aid of an electric cart. The third was diagnosed by ultrasound, and pregnancy was terminated at 30 weeks' gestation. The lumbar spine of the mother was interpreted as showing early osteoporosis; the age of the parents was not given. Studies in the children showed overhydroxylation of type I collagen components over the entire length of the collagen and procollagen triple helix, suggesting overmodification of type I collagen. Linkage studies excluded both the COL1A1 (120150) and the COL1A2 (120160) genes as the site of the mutation in this disorder (Daw et al., 1988). Van Dijk et al. (2009) studied 2 fetuses with osteogenesis imperfecta from a nonconsanguineous northern European family; radiographs and autopsy at 16 weeks' and 22 weeks' gestation, respectively, showed absence of rib fractures with shortened, bowed, and fractured long bones without evidence of rhizomelia, consistent with a diagnosis of Sillence OI type II. Weight and head circumference were normal for gestational age, and no other abnormalities were noted. Bone histology confirmed the diagnosis of OI, and overmodification of collagen type I in fibroblasts was evident on electrophoresis. Van Dijk et al. (2009) also studied 2 sibs with OI from a consanguineous Pakistani family, the older of whom was born with multiple long-bone fractures and had a large head with large anterior fontanel and gray-colored sclerae, flexed and abducted hips, short bowed femurs with anterior bowing of the tibiae, and joint hypermobility, especially of the finger and hip joints, consistent with a diagnosis of Sillence OI type III. There was no evidence of dentinogenesis imperfecta. The older sib, who had never walked, used a wheelchair at age 8 years and had kyphoscoliosis of the thoracic and lumbar spine, with a height at the 50th percentile for a 17-month-old child. Barnes et al. (2010) studied a 4-year-old girl and her 12-year-old brother, born of consanguineous Senegalese parents, who had moderately severe osteogenesis imperfecta. The affected sibs did not have rhizomelia or severe deformity of the long bones, and their skin was normal in appearance and extensibility. Although they had moderate axial growth deficiency, their hand length and segmental proportions were appropriate for their age. Both children had white sclerae and normal dentition. The brother, whose osteogenesis imperfecta was milder than that of his sister, also had sickle cell disease.
In 4 patients from 2 unrelated families with severe osteogenesis imperfecta, van Dijk et al. (2009) analyzed the PPIB gene and identified homozygosity for a frameshift (123841.0001) and a nonsense (123841.0002) mutation, respectively.
In a sister ... In 4 patients from 2 unrelated families with severe osteogenesis imperfecta, van Dijk et al. (2009) analyzed the PPIB gene and identified homozygosity for a frameshift (123841.0001) and a nonsense (123841.0002) mutation, respectively. In a sister and brother who had moderately severe osteogenesis imperfecta without rhizomelia, who were born of consanguineous Senegalese parents, Barnes et al. (2010) identified homozygosity for a missense mutation in the PPIB gene (123841.0003). The proband had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CYPB is not the exclusive peptidyl-prolyl cis-trans isomerase that catalyzes the rate-limiting step in collagen folding. In a Palestinian pedigree segregating moderate and lethal forms of OI, Barnes et al. (2012) identified a homozygous indel mutation in the FKBP10 gene (607063.0009) in a proband from one branch of the family with OI type 11 (610968), and a homozygous deletion in the PPIB gene (123841.0004) in a proband from another branch of the family with OI type IX (259940).