RGD Reference Report - Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I. - Rat Genome Database

RGD Reference Report - Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I. - Rat Genome Database

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Order of intron removal influences multiple splice outcomes, including a two-exon skip, in a COL5A1 acceptor-site mutation that results in abnormal pro-alpha1(V) N-propeptides and Ehlers-Danlos syndrome type I.
Authors:	Takahara, K Schwarze, U Imamura, Y Hoffman, GG Toriello, H Smith, LT Byers, PH Greenspan, DS
Citation:	Takahara K, etal., Am J Hum Genet. 2002 Sep;71(3):451-65. Epub 2002 Jul 17.
RGD ID:	1581210
Pubmed:	PMID:12145749 (View Abstract at PubMed)
PMCID:	PMC379186 (View Article at PubMed Central)
DOI:	DOI:10.1086/342099 (Journal Full-text)
Ehlers-Danlos syndrome (EDS) type I (the classical variety) is a dominantly inherited, genetically heterogeneous connective-tissue disorder. Mutations in the COL5A1 and COL5A2 genes, which encode type V collagen, have been identified in several individuals. Most mutations affect either the triple-helical domain of the protein or the expression of one COL5A1 allele. We identified a novel splice-acceptor mutation (IVS4-2A-->G) in the N-propeptide-encoding region of COL5A1, in one patient with EDS type I. The outcome of this mutation was complex: In the major product, both exons 5 and 6 were skipped; other products included a small amount in which only exon 5 was skipped and an even smaller amount in which cryptic acceptor sites within exon 5 were used. All products were in frame. Pro-alpha1(V) chains with abnormal N-propeptides were secreted and were incorporated into extracellular matrix, and the mutation resulted in dramatic alterations in collagen fibril structure. The two-exon skip occurred in transcripts in which intron 5 was removed rapidly relative to introns 4 and 6, leaving a large (270 nt) composite exon that can be skipped in its entirety. The transcripts in which only exon 5 was skipped were derived from those in which intron 6 was removed prior to intron 5. The use of cryptic acceptor sites in exon 5 occurred in transcripts in which intron 4 was removed subsequent to introns 5 and 6. These findings suggest that the order of intron removal plays an important role in the outcome of splice-site mutations and provide a model that explains why multiple products derive from a mutation at a single splice site.

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
COL5A1	Human	Ehlers-Danlos syndrome		IAGP			RGD
Col5a1	Rat	Ehlers-Danlos syndrome		ISO	RGD:733435		RGD
Col5a1	Mouse	Ehlers-Danlos syndrome		ISO	RGD:733435		RGD

Genes (Rattus norvegicus)


Col5a1 (collagen type V alpha 1 chain)

Genes (Mus musculus)


Col5a1 (collagen, type V, alpha 1)

Genes (Homo sapiens)


COL5A1 (collagen type V alpha 1 chain)