Title |
Deletion of exon 8 from the EXT1 gene causes multiple osteochondromas (MO) in a family with three affected members
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Published in |
SpringerPlus, January 2016
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DOI | 10.1186/s40064-016-1695-6 |
Pubmed ID | |
Authors |
Lei Zhuang, Simon D. Gerber, Stefan Kuchen, Peter M. Villiger, Beat Trueb |
Abstract |
Multiple osteochondromas (also called hereditary multiple exostoses) is an autosomal dominant disorder characterized by multiple cartilaginous tumors, which are caused by mutations in the genes for exostosin-1 (EXT1) and exostosin-2 (EXT2). The goal of this study was to elucidate the genetic alterations in a family with three affected members. Isolation of RNA from the patients' blood followed by reverse transcription and PCR amplification of selected fragments showed that the three patients lack a specific region of 90 bp from their EXT1 mRNA. This region corresponds to the sequence of exon 8 from the EXT1 gene. No splice site mutation was found around exon 8. However, long-range PCR amplification of the region from intron 7 to intron 8 indicated that the three patients contain a deletion of 4318 bp, which includes exon 8 and part of the flanking introns. There is evidence that the deletion was caused by non-homologous end joining because the breakpoints are not located within a repetitive element, but contain multiple copies of the deletion hotspot sequence TGRRKM. Exon 8 encodes part of the active site of the EXT1 enzyme, including the DXD signature of all UDP-sugar glycosyltransferases. It is conceivable that the mutant protein exerts a dominant negative effect on the activity of the EXT glycosyltransferase since it might interact with normal copies of the enzyme to form an inactive hetero-oligomeric complex. We suggest that sequencing of RNA might be superior to exome sequencing to detect short deletions of a single exon. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 3 | 23% |
Other | 2 | 15% |
Student > Bachelor | 2 | 15% |
Lecturer | 1 | 8% |
Student > Ph. D. Student | 1 | 8% |
Other | 3 | 23% |
Unknown | 1 | 8% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 31% |
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Immunology and Microbiology | 1 | 8% |
Unknown | 1 | 8% |