Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): Review and report on the first North American case

McPherson, Elizabeth; Clemens, Michele

doi:10.1002/(sici)1096-8628(19970502)70:1<28::aid-ajmg6>3.0.co;2-n

Cited by 46 publications

(20 citation statements)

References 3 publications

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“…A few cases had dysmorphic features including triangular face and brachycephaly [13][14][15][16][17][18][19]. Most BS cases OPIS PRZYPADKU Table I Nl treated with pamidronate had good to fair response.…”

Section: Discussionmentioning

confidence: 99%

Zespół Brucka — rzadki zespół charakteryzujący się kruchością kości, przykurczami stawowymi i nowoodkrytą homozygotyczną mutacją FKBP10

Moravej

Karamifar

Karamizadeh

et al. 2015

Endokrynologia Polska

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Bruck syndrome is an autosomal recessive syndrome consisting of bone fragility and congenital joint contractures. According to the genotype, it has been classified into types 1 and 2. Recently, mutations in FKBP10, localised to chromosome 17q21, have been identified in some patients of Bruck syndrome. Twenty-seven patients of this syndrome have been reported so far. We present a new patient of this syndrome, with frequent fractures, congenital joint contractures, kyphoscoliosis, bilateral clubfoot, and pectus carinatum. The clinical and genetic features of all previously reported cases are also reviewed.

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Section: Discussionmentioning

confidence: 99%

Zespół Brucka — rzadki zespół charakteryzujący się kruchością kości, przykurczami stawowymi i nowoodkrytą homozygotyczną mutacją FKBP10

Moravej

Karamifar

Karamizadeh

et al. 2015

Endokrynologia Polska

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“…Bruck syndrome (BS; Online Mendelian Inheritance in Man (OMIM) accession number 259450), an autosomal recessive disease, is characterized by osteoporosis, joint contractures at birth, fragile bones, and short stature (25)(26)(27)(28). Biochemical analysis of the bone of BS patients revealed an underhydroxylation of lysine residues in the telopeptides of collagen type I, whereas hydroxylation of lysine residues in the triple helix is normal (29).…”

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confidence: 99%

Identification of PLOD2 as Telopeptide Lysyl Hydroxylase, an Important Enzyme in Fibrosis

Slot¹,

Zuurmond²,

Bardoel

et al. 2003

Journal of Biological Chemistry

366

329

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The hallmark of fibrotic processes is an excessive accumulation of collagen. The deposited collagen shows an increase in pyridinoline cross-links, which are derived from hydroxylated lysine residues within the telopeptides. This change in cross-linking is related to irreversible accumulation of collagen in fibrotic tissues. The increase in pyridinoline cross-links is likely to be the result of increased activity of the enzyme responsible for the hydroxylation of the telopeptides (telopeptide lysyl hydroxylase, or TLH). Although the existence of TLH has been postulated, the gene encoding TLH has not been identified. By analyzing the genetic defect of Bruck syndrome, which is characterized by a pyridinoline deficiency in bone collagen, we found two missense mutations in exon 17 of PLOD2, thereby identifying PLOD2 as a putative TLH gene. Subsequently, we investigated fibroblasts derived from fibrotic skin of systemic sclerosis (SSc) patients and found that PLOD2 mRNA is highly increased indeed. Furthermore, increased pyridinoline cross-link levels were found in the matrix deposited by SSc fibroblasts, demonstrating a clear link between mRNA levels of the putative TLH gene (PLOD2) and the hydroxylation of lysine residues within the telopeptides. These data underscore the significance of PLOD2 in fibrotic processes.The biosynthesis of collagen molecules involves several intracellular post-translational modifications followed by excretion and extracellular aggregation of the collagen molecules into fibrils, which are subsequently stabilized by intermolecular cross-links (1, 2). Two related routes are responsible for the formation of these collagen cross-links, namely the allysine route, in which a lysine residue in the telopeptide is converted by lysyl oxidase into the aldehyde allysine, and the hydroxyallysine route, in which a hydroxylysine residue in the telopeptide is converted into the aldehyde hydroxyallysine. Subsequently, the allysine or the hydroxyallysine reacts with a Lys or Hyl residue in the triple helix to form di-, tri-, or tetrafunctional cross-links (3-6). The mature cross-links hydroxylysylpyridinoline or lysylpyridinoline are formed via the hydroxyallysine route and occur in a variety of connective tissues such as bone, tendon, ligaments, and cartilage (7). In contrast, collagen in the skin is mainly cross-linked via the allysine route. Interestingly, in fibrotic skin (lipodermatosclerosis, keloid) and organ fibrosis (lung, liver), which is characterized by an excessive accumulation of collagen, an increase in crosslinks derived from the hydroxyallysine route is found (8 -15). It has been shown that the amount of hydroxyallysine-derived cross-links is related to the irreversible accumulation of collagen in fibrotic tissues, indicating that collagen containing hydroxyallysine-derived cross-links is more difficult to degrade than collagen containing allysine-derived cross-links (10 -12, 14, 15). Inhibition of the formation of hydroxyallysine-derived cross-links in fibrosis is therefore likely to resu...

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“…Worldwide only nine families (comprising 14 patients) have been reported (22-27). Although an abnormality in the bone collagen network in BS was assumed, the underlying defect remained unknown: collagen in bone and the collagen synthesized by cultured skin fibroblasts showed none of the changes commonly found in osteogenesis imperfecta (23,(26)(27)). Here we report that the molecular defect underlying BS is a deficiency of bone-specific TLH, which results in aberrant crosslinking of bone collagen.…”

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confidence: 99%

“…A reduction of mineral content and an increase in size of the hydroxyapatite crystals were observed (23). Worldwide only nine families (comprising 14 patients) have been reported (22)(23)(24)(25)(26)(27). Although an abnormality in the bone collagen network in BS was assumed, the underlying defect remained unknown: collagen in bone and the collagen synthesized by cultured skin fibroblasts showed none of the changes commonly found in osteogenesis imperfecta (23,(26)(27).…”

mentioning

confidence: 99%

Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17

Bank

Robins

Wijmenga

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

178

165

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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.Collagen fibrils are important for the mechanical strength of bone (1-2). The tensile properties of fibrils result from intermolecular crosslinks connecting the nonhelical ends of a collagen molecule (telopeptides) with the triple helical part of an adjacent molecule (2-3). More than ten different collagen crosslinks are known; their structure, number, and location are highly tissue specific and not related to a specific collagen type (4-8). Stereochemical and x-ray diffraction studies revealed that differences in molecular packing of collagen within fibrils are associated with differences in crosslink profiles (9-12). Proper mineralization probably depends on a correct alignment of collagen molecules, as nucleation of calcium apatite crystals starts in the gap region, i.e., in the area adjacent to the crosslink site (9). Alterations in crosslink patterns associated with changes in the molecular packing are, therefore, expected to result in aberrant mineralization.Residues involved in crosslinking are mainly the amino acids lysine (Lys) or hydroxylysine (Hyl) (4-8). The enzyme lysyl hydroxylase (LH) (procollagen-lysine, 2-oxoglutarate 5-dioxygenase; EC 1.14.11.4) catalyzes the conversion of Lys into Hyl (13-15). Crosslinking is initiated only after specific Lys or Hyl residues of the telopeptides are converted extracellularly by the enzyme lysyl oxidase into the aldehydes allysine and hydroxyallysine, respectively (4-8). The aldehydes subsequently react with Lys, Hyl, or histidyl, residues of the triple helix to give characteristic di-, tri-, and tetrafunctional crosslinks. Two related routes for the formation of crosslinks have been described, based on ...

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Bruck syndrome (osteogenesis imperfecta with congenital joint contractures): Review and report on the first North American case

Cited by 46 publications

References 3 publications

Zespół Brucka — rzadki zespół charakteryzujący się kruchością kości, przykurczami stawowymi i nowoodkrytą homozygotyczną mutacją FKBP10

Zespół Brucka — rzadki zespół charakteryzujący się kruchością kości, przykurczami stawowymi i nowoodkrytą homozygotyczną mutacją FKBP10

Identification of PLOD2 as Telopeptide Lysyl Hydroxylase, an Important Enzyme in Fibrosis

Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: Indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17

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