Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/7346
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cox, T. | - |
dc.contributor.author | Allen, L. | - |
dc.contributor.author | Cox, L. | - |
dc.contributor.author | Hopwood, B. | - |
dc.contributor.author | Goodwin, B. | - |
dc.contributor.author | Haan, E. | - |
dc.contributor.author | Suthers, G. | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Human Molecular Genetics, 2000; 9(17):2553-2562 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.issn | 1460-2083 | - |
dc.identifier.uri | http://hdl.handle.net/2440/7346 | - |
dc.description | Copyright © 2000 Oxford University Press | - |
dc.description.abstract | Opitz syndrome (OS) is a genetically heterogeneous malformation disorder. Patients with OS may present with a variable array of malformations that are indicative of a disturbance of the primary midline developmental field. Mutations in the C-terminal half of MID1, an RBCC (RING, B-box and coiled-coil) protein, have recently been shown to underlie the X-linked form of OS. Here we show that the MID1 gene spans at least 400 kb, almost twice the distance originally reported and has a minimum of six mRNA isoforms as a result of the alternative use of 5' untranslated exons. In addition, our detailed mutational analysis of MID1 in a cohort of 15 patients with OS has resulted in the identification of seven novel mutations, two of which disrupt the N-terminus of the protein. The most severe of these (E115X) is predicted to truncate the protein before the B-box motifs. In a separate patient, a missense change (L626P) was found that also represents the most C-terminal alteration reported to date. As noted with other C-terminal mutations, GFP fusion constructs demonstrated that the L626P mutant formed cytoplasmic clumps in contrast to the microtubular distribution seen with the wild-type sequence. Notably, however, both N-terminal mutants showed no evidence of cytoplasmic aggregation, inferring that this feature is not pathognomonic for X-linked OS. These new data and the finding of linkage to MID1 in the absence of a demonstrable open reading frame mutation in a further family support the conclusion that X-linked OS results from loss of function of MID1. | - |
dc.description.statementofresponsibility | Timothy C. Cox, Lillian R. Allen, Liza L. Cox, Blair Hopwood, Bruce Goodwin, Eric Haan and Graeme K. Suthers | - |
dc.language.iso | en | - |
dc.publisher | Oxford Univ Press | - |
dc.source.uri | http://hmg.oxfordjournals.org/cgi/content/full/9/17/2553 | - |
dc.subject | X Chromosome | - |
dc.subject | Cell Nucleus | - |
dc.subject | Cytoplasm | - |
dc.subject | Microtubules | - |
dc.subject | Humans | - |
dc.subject | Abnormalities, Multiple | - |
dc.subject | Syndrome | - |
dc.subject | Microtubule Proteins | - |
dc.subject | Ubiquitin-Protein Ligases | - |
dc.subject | Nuclear Proteins | - |
dc.subject | Recombinant Fusion Proteins | - |
dc.subject | Transcription Factors | - |
dc.subject | DNA, Complementary | - |
dc.subject | Codon, Nonsense | - |
dc.subject | Pedigree | - |
dc.subject | Amino Acid Motifs | - |
dc.subject | Zinc Fingers | - |
dc.subject | Mutation | - |
dc.subject | Mutation, Missense | - |
dc.subject | Open Reading Frames | - |
dc.subject | Exons | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.subject | Genetic Linkage | - |
dc.title | New mutations in MID1 provide support for loss of function as the cause of X-linked Optiz syndrome | - |
dc.type | Journal article | - |
dc.contributor.organisation | Centre for the Molecular Genetics of Development | - |
dc.identifier.doi | 10.1093/hmg/9.17.2553 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Haan, E. [0000-0002-7310-5124] | - |
Appears in Collections: | Aurora harvest 5 Centre for the Molecular Genetics of Development publications Paediatrics publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_7346.pdf | 660.89 kB | Publisher's PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.