Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2

Détails

ID Serval
serval:BIB_238317094008
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Phenotypic and molecular characterization of Bruck syndrome (osteogenesis imperfecta with contractures of the large joints) caused by a recessive mutation in PLOD2
Périodique
American Journal of Medical Genetics. Part A
Auteur(s)
Ha-Vinh  R., Alanay  Y., Bank  R. A., Campos-Xavier  A. B., Zankl  A., Superti-Furga  A., Bonafe  L.
ISSN
1552-4825
Statut éditorial
Publié
Date de publication
12/2004
Peer-reviewed
Oui
Volume
131
Numéro
2
Pages
115-20
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 1
Résumé
Bruck syndrome (BS) is a recessively-inherited phenotypic disorder featuring the unusual combination of skeletal changes resembling osteogenesis imperfecta (OI) with congenital contractures of the large joints. Clinical heterogeneity is apparent in cases reported thus far. While the genes coding for collagen 1 chains are unaffected in BS, there is biochemical evidence for a defect in the hydroxylation of lysine residues in collagen 1 telopeptides. One BS locus has been mapped at 17p12, but more recently, two mutations in the lysyl hydroxylase 2 gene (PLOD2, 3q23-q24) have been identified in BS, showing genetic heterogeneity. The proportion of BS cases linked to 17p22 (BS type 1) or caused by mutations in PLOD2 (BS type 2) is still uncertain, and phenotypic correlations are lacking. We report on a boy who had congenital contractures with pterygia at birth and severe OI-like osteopenia and multiple fractures. His urine contained high amounts of hydroxyproline but low amounts of collagen crosslinks degradation products; and he was shown to be homozygous for a novel mutation leading to an Arg598His substitution in PLOD2. The mutation is adjacent to the two mutations previously reported (Gly601Val and Thr608Ile), suggesting a functionally important hotspot in PLOD2. The combination of pterygia with bone fragility, as illustrated by this case, is difficult to explain; it suggests that telopeptide lysyl hydroxylation must be involved in prenatal joint formation and morphogenesis. Collagen degradation products in urine and mutation analysis of PLOD2 may be used to diagnose BS and differentiate it from OI.
Mots-clé
Abnormalities, Multiple/*genetics/radiography Amino Acid Sequence Child, Preschool Collagen/urine Consanguinity Contracture/*genetics Elbow Joint/*abnormalities/radiography Fractures, Bone/genetics Genes, Recessive Humans Hydroxyproline/urine Knee Joint/*abnormalities/radiography Male Molecular Sequence Data *Mutation Osteogenesis Imperfecta/*genetics/radiography Phenotype Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/*genetics Syndrome
Pubmed
Web of science
Création de la notice
21/01/2008 13:50
Dernière modification de la notice
03/03/2018 14:54
Données d'usage