Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia

Glazov, Evgeny A., Zankl, Andreas, Donskoi, Marina, Kenna, Tony J., Thomas, Gethin P., Clark, Graeme R., Duncan, Emma L., & Brown, Matthew A. (2011) Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia. PLoS Genetics, 7(3), Article Number:-e1002027.

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Recent advances in DNA sequencing have enabled mapping of genes for monogenic traits in families with small pedigrees and even in unrelated cases. We report the identification of disease-causing mutations in a rare, severe, skeletal dysplasia, studying a family of two healthy unrelated parents and two affected children using whole-exome sequencing. The two affected daughters have clinical and radiographic features suggestive of anauxetic dysplasia (OMIM 607095), a rare form of dwarfism caused by mutations of RMRP. However, mutations of RMRP were excluded in this family by direct sequencing. Our studies identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing (RNase MRP) complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia. We demonstrate that these mutations impair the integrity and activity of this complex and that they impair cell proliferation, providing likely molecular and cellular mechanisms by which POP1 mutations cause this severe skeletal dysplasia. © 2011 Glazov et al.

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ID Code: 94210
Item Type: Journal Article
Refereed: Yes
Keywords: cytoskeleton protein, mitochondrial RNA, protein POP1, ribonuclease, unclassified drug, apoptosis regulatory protein, POP1 protein, human, ribonucleoprotein, RNA 5.8S, anauxetic dysplasia, article, bone dysplasia, child, complex formation, controlled study, disease severity, exome, family assessment, gene identification, gene interaction, gene mutation, gene sequence, genetic polymorphism, heterozygosity loss, human, human cell, loss of function mutation, molecular dynamics, nucleotide sequence, sequence analysis, case report, cell proliferation, DNA sequence, exon, female, genetics, infant, male, metabolism, molecular genetics, mononuclear cell, mutation, pathology, pedigree, single nucleotide polymorphism, Apoptosis Regulatory Proteins, Bone Diseases, Developmental, Exons, Humans, Leukocytes, Mononuclear, Molecular Sequence Data, Polymorphism, Single Nucleotide, Ribonucleoproteins, RNA, Ribosomal, 5.8S, Sequence Analysis, DNA
DOI: 10.1371/journal.pgen.1002027
ISSN: 1553-7390
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 29 Mar 2016 00:03
Last Modified: 24 Nov 2016 02:23

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