Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/6912
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Type: Journal article
Title: A recurrent RNA-splicing mutation in the SEDL gene causes X-linked spondyloepiphyseal dysplasia tarda
Author: Tiller, G.
Hannig, V.
Dozier, D.
Carrel, L.
Trevarthen, K.
Wilcox, W.
Mundlos, S.
Haines, J.
Gedeon, A.
Gecz, J.
Citation: American Journal of Human Genetics, 2001; 68(6):1398-1407
Publisher: Univ Chicago Press
Issue Date: 2001
ISSN: 0002-9297
1537-6605
Statement of
Responsibility: 
Tiller, George E. ; Hannig, Vickie L. ; Dozier, Damon ; Carrel, Laura ; Trevarthen, Karrie C. ; Wilcox, William R. ; Mundlos, Stefan ; Haines, Jonathan L. ; Gedeon, Agi K. ; Gecz, Jozef
Abstract: Spondyloepiphyseal dysplasia tarda (SEDL) is a genetically heterogeneous disorder characterized by mild-to-moderate short stature and early-onset osteoarthritis. Both autosomal and X-linked forms have been described. Elsewhere, we have reported the identification of the gene for the X-linked recessive form, which maps to Xp22.2. We now report characterization of an exon-skipping mutation (IVS3+5G-->A at the intron 3 splice-donor site) in two unrelated families with SEDL. Using reverse transcriptase (RT)-PCR, we demonstrated that the mutation resulted in elimination of the first 31 codons of the open reading frame. The mutation was not detected in 120 control X chromosomes. Articular cartilage from an adult who had SEDL and carried this mutation contained chondrocytes with abundant Golgi complexes and dilated rough endoplasmic reticulum (ER). RT-PCR experiments using mouse/human cell hybrids revealed that the SEDL gene escapes X inactivation. Homologues of the SEDL gene include a transcribed retropseudogene on chromosome 19, as well as expressed genes in mouse, rat, Drosophila melanogaster Caenorhabditis elegans, and Saccharomyces cerevisiae. The latter homologue, p20, has a putative role in vesicular transport from ER to Golgi complex. These data suggest that SEDL mutations may perturb an intracellular pathway that is important for cartilage homeostasis.
Keywords: Cartilage
Cells, Cultured
Hybrid Cells
X Chromosome
Endoplasmic Reticulum, Rough
Golgi Apparatus
Chondrocytes
Animals
Humans
Osteochondrodysplasias
Carrier Proteins
Membrane Transport Proteins
Transcription Factors
RNA, Messenger
RNA Splice Sites
Pedigree
DNA Mutational Analysis
RNA Splicing
Base Sequence
Consensus Sequence
Protein Transport
Phenotype
Mutation
Exons
Molecular Sequence Data
Adult
Middle Aged
Dosage Compensation, Genetic
Female
Male
Genetic Linkage
DOI: 10.1086/320594
Appears in Collections:Aurora harvest 5
Paediatrics publications

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