Dataset Information

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta.

ABSTRACT: BACKGROUND:Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. METHODS:The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures. RESULTS:Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. CONCLUSIONS:Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.

SUBMITTER: Steinlein OK

PROVIDER: S-EPMC3270005 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta.

Steinlein Ortrud K OK Aichinger Eric E Trucks Holger H Sander Thomas T

BMC medical genetics 20111122

<h4>Background</h4>Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis.<h4>Methods</h4>The patients described here are af ...[more]

PMID: 22107750

Similar Datasets

Project description:BACKGROUND:Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. CASE PRESENTATION:Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A?>?G, IVS7-2A?>?G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. CONCLUSIONS:Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations.

Dataset Information

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta.

Publications

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets