Van Dijk et al. (2013) studied 5 families with X-linked osteoporosis and osteoporotic fractures. The majority of hemizygous male family members presented with osteoporosis and fractures of the axial and appendicular skeleton developing in childhood, whereas the clinical ... Van Dijk et al. (2013) studied 5 families with X-linked osteoporosis and osteoporotic fractures. The majority of hemizygous male family members presented with osteoporosis and fractures of the axial and appendicular skeleton developing in childhood, whereas the clinical picture in heterozygous women ranged from normal bone density and an absence of fractures to early-onset osteoporosis and vertebral compression fractures on x-ray. Some family members exhibited joint hypermobility, but no other features of osteogenesis imperfecta (see 166200) were present.
Van Dijk et al. (2013) performed X-linked whole-exome sequencing in 3 affected male patients from a 3-generation family with osteoporosis and fractures, and identified hemizygosity for a 1-bp deletion in the PLS3 gene (300131.0001); Sanger sequencing confirmed that ... Van Dijk et al. (2013) performed X-linked whole-exome sequencing in 3 affected male patients from a 3-generation family with osteoporosis and fractures, and identified hemizygosity for a 1-bp deletion in the PLS3 gene (300131.0001); Sanger sequencing confirmed that the mutation segregated with disease in the family. Sequencing PLS3 in 95 male patients who were referred for diagnosis or exclusion of osteogenesis imperfecta type I (OI1; 166200), who were known to be negative for mutation in the COL1A1 (120150) or COL1A2 (120160) genes, revealed pathogenic variants in 4 probands (see, e.g., 300131.0002). In addition, a PLS3 variant (dbSNP rs140121121; 300131.0003) was identified in 5 of the 95 patients referred for possible OI1; the variant was also associated with a 2-fold increased risk of fracture among elderly heterozygous women compared to noncarriers.