ABSTRACT
Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament show unaltered telopeptide hydroxylation as evidenced by normal patterns of crosslinking. The results provide compelling evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. This new family of enzymes appears to provide the primary regulation for controlling the different pathways of collagen crosslinking and explains why crosslink patterns are tissue specific and not related to a genetic collagen type. A genome screen identified only a single region on chromosome 17p12 where all affected sibs shared a cluster of haplotypes identical by descent; this might be the BS (Bruck syndrome) locus and consequently the region where bone telopeptidyl lysyl hydroxylase is located. Further knowledge of this enzyme has important implications for conditions where aberrant expression of telopeptide lysyl hydroxylase occurs, such as fibrosis and scar formation.
Subject(s)
Bone Diseases/genetics , Bone and Bones/metabolism , Chromosomes, Human, Pair 17 , Collagen/metabolism , Contracture/genetics , Growth Disorders/genetics , Osteoporosis/genetics , Peptides/metabolism , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Adolescent , Child , Child, Preschool , Chromosome Mapping , Collagen Type I , Consanguinity , Female , Genetic Markers , Genome, Human , Genotype , Homozygote , Humans , Ligaments/metabolism , Male , Pedigree , SyndromeABSTRACT
We examined in a cross-sectional study, 47 children (mean age 7.7 (1-16) years) with osteogenesis imperfecta (OI) to find the prevalence of spinal deformities and to correlate these observations with anthropometry. The associations between dentinogenesis imperfecta, joint hypermobility and spinal deformities were also studied. Disproportion in stature in OI type I and type IV was mainly caused by spinal involvement, as evidenced by a greater decrease in body height than in leg length. In OI type I, the decrease in sitting height was mainly caused by platyspondyly, whereas in OI types III and IV, it was also caused by progressive scoliosis and kyphosis. Scoliosis was present in 22 children, and pathological kyphosis in 18, mainly in the severe OI types. Basilar impression was observed in 10 children, mainly in type III. Children with dentinogenesis imperfecta seemed to be prone to develop scoliosis, pathological kyphosis and basilar impression. Children with generalized joint hypermobility were less prone to develop scoliosis and basilar impression. Our observations may contribute to a better understanding of the risk factors for progressive spinal deformities in OI.
Subject(s)
Anthropometry , Kyphosis/epidemiology , Osteogenesis Imperfecta/complications , Scoliosis/epidemiology , Spine/abnormalities , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Joint Instability/epidemiology , Joint Instability/etiology , Kyphosis/etiology , Male , Prevalence , Risk Factors , Scoliosis/etiologyABSTRACT
The trisomy 8 mosaic syndrome may present in many different ways. We present a rare hair anomaly in a patient with this syndrome.
