1193 BIOCHEMICAL HETEROGENEITY OF
OSTEOGENESIS IMPERFECTA: NEW VARIANT
SiR,—Osteogenesis imperfecta (0.1.) is an inherited connective-tissue defect characterised by fragile, poorly calcified bones. Fractures occur in prenatal or perinatal life (0.1. congenita) or later (0.1. tarda). The defect is not confined to bone because blue sclerx, widespread hernias, loose jointedness, and soft, silky skin are common The biochemical basis of 0.1. has lately become clearer. For example, Penttinen et a1.2 showed that the ratio of the genetically distinct type i collagen to type III collagen was much reduced in radio-labelled skin fibroblasts from a baby with broad-boned lethal 0.1. whereas Trelstad et al.,’ studying both tissues and fibroblasts from a similar patient, observed normal ratios of 1:111 but noted that more lysine residues were hydroxylated than normal. Sykes et al. studying skin have found reduced i:m ratios in mild 0.1. tarda. We have investigated a patient with a different biochemical defect. Skin fibroblasts
were
cultured from
a
21-month-male with mode-
rately severe 0.1. born to normal consanguineous parents. Collagens were biosynthetically labelled with 14C-proline and 14C-glycine and the secreted proteins digested with pepsin in 0.5 mol/l acetic acid which removes globular proteins and the extension peptides of procollagen but leaves the collagen helix intact. The pepsin-resistant proteins were analysed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate.5 The gels were sliced and assayed for radioactivity by scintillation counting after solubilisation wilh hydrogen peroxide figure). Control cell lines show
a
normal al:a2 ratio of 2:1 but the
patient has only a single, possibly broader, peak in the ocl position and nothing in the a2 position. Type-i collagen, which is the major component of bone, skin, and tendon, is a triple-
Electrophoretogram
stranded molecule with two al chains and one
OSTEOGENESIS IMPERFECTA: NEW VARIANT
SiR,—Osteogenesis imperfecta (0.1.) is an inherited connective-tissue defect characterised by fragile, poorly calcified bones. Fractures occur in prenatal or perinatal life (0.1. congenita) or later (0.1. tarda). The defect is not confined to bone because blue sclerx, widespread hernias, loose jointedness, and soft, silky skin are common The biochemical basis of 0.1. has lately become clearer. For example, Penttinen et a1.2 showed that the ratio of the genetically distinct type i collagen to type III collagen was much reduced in radio-labelled skin fibroblasts from a baby with broad-boned lethal 0.1. whereas Trelstad et al.,’ studying both tissues and fibroblasts from a similar patient, observed normal ratios of 1:111 but noted that more lysine residues were hydroxylated than normal. Sykes et al. studying skin have found reduced i:m ratios in mild 0.1. tarda. We have investigated a patient with a different biochemical defect. Skin fibroblasts
were
cultured from
a
21-month-male with mode-
rately severe 0.1. born to normal consanguineous parents. Collagens were biosynthetically labelled with 14C-proline and 14C-glycine and the secreted proteins digested with pepsin in 0.5 mol/l acetic acid which removes globular proteins and the extension peptides of procollagen but leaves the collagen helix intact. The pepsin-resistant proteins were analysed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate.5 The gels were sliced and assayed for radioactivity by scintillation counting after solubilisation wilh hydrogen peroxide figure). Control cell lines show
a
normal al:a2 ratio of 2:1 but the
patient has only a single, possibly broader, peak in the ocl position and nothing in the a2 position. Type-i collagen, which is the major component of bone, skin, and tendon, is a triple-
Electrophoretogram
stranded molecule with two al chains and one
