Biomaterial Database

Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome--osteogenesis imperfecta phenotypic spectrum. 2012

Maria Trinidad Puig-Hervás, and Samia Temtamy, and Mona Aglan, and Maria Valencia, and Víctor Martínez-Glez, and María Juliana Ballesta-Martínez, and Vanesa López-González, and Adel M Ashour, and Khalda Amr, and Veronica Pulido, and Encarna Guillén-Navarro, and Pablo Lapunzina, and José A Caparrós-Martín, and Victor L Ruiz-Perez

Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.

PLOD2 and FKBP10 are genes mutated in Bruck syndrome (BS), a condition resembling osteogenesis imperfecta (OI), but that is also typically associated with congenital joint contractures. Herein, we sought mutations in six consanguineous BS families and detected changes in either PLOD2 or FKBP10 in all cases. Two probands were found with a homozygous frameshift mutation in the alternative exon 13a of PLOD2, indicating that specific inactivation of the longer protein isoform encoded by this gene is sufficient to cause BS. In addition, by homozygosity mapping, followed by a candidate gene approach, we identified a homozygous donor splice site mutation in PLOD2 in a patient with autosomal-recessive OI (AR-OI). Screening of additional samples also revealed compound heterozygous mutations in PLOD2 in two brothers, one affected with mild AR-OI and the other with mild BS. Thus, PLOD2 in addition to causing BS is also associated with AR-OI phenotypes of variable severity.

UI	MeSH Term	Description	Entries
D008240	Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase	A mixed-function oxygenase that catalyzes the hydroxylation of peptidyllysine, usually in protocollagen, to peptidylhydroxylysine. The enzyme utilizes molecular oxygen with concomitant oxidative decarboxylation of the cosubstrate 2-oxoglutarate to succinate. EC 1.14.11.4.	Lysine 2-Oxoglutarate Dioxygenase,Lysine Hydroxylase,Protocollagen Lysyl Hydroxylase,Collagen Lysyl Hydroxylase,Lysyl Hydroxylase,2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine,2-Oxoglutarate Dioxygenase, Lysine,5-Dioxygenase Procollagen-Lysine, 2-Oxoglutarate,Dioxygenase, Lysine 2-Oxoglutarate,Hydroxylase, Collagen Lysyl,Hydroxylase, Lysine,Hydroxylase, Lysyl,Hydroxylase, Protocollagen Lysyl,Lysine 2 Oxoglutarate Dioxygenase,Procollagen Lysine, 2 Oxoglutarate 5 Dioxygenase
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010013	Osteogenesis Imperfecta	COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.	Fragilitas Ossium,Lobstein Disease,Brittle Bone Disease,Lobstein's Disease,Osteogenesis Imperfecta Tarda,Osteogenesis Imperfecta with Blue Sclerae,Osteogenesis Imperfecta, Type 1,Osteogenesis Imperfecta, Type I,Disease, Lobstein,Disease, Lobstein's,Lobsteins Disease,Ossiums, Fragilitas,Osteogenesis Imperfecta Tardas
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D003240	Connective Tissue Diseases	A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.	Connective Tissue Disease,Disease, Connective Tissue,Diseases, Connective Tissue
D003241	Consanguinity	The magnitude of INBREEDING in humans.	Inbreeding, Human,Consanguineous Marriage,Consanguinous Mating,Consanguineous Marriages,Consanguinities,Consanguinous Matings,Human Inbreeding,Human Inbreedings,Inbreedings, Human,Marriage, Consanguineous,Marriages, Consanguineous,Mating, Consanguinous,Matings, Consanguinous