ArticleAmerican journal of human genetics1999
Congenital end-plate acetylcholinesterase deficiency caused by a nonsense mutation and an A-->G splice-donor-site mutation at position +3 of the collagenlike-tail-subunit gene (COLQ): how does G at position +3 result in aberrant splicing?
Article in American journal of human genetics, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Pharmacological Treatments for Congenital Myasthenic Syndromes Caused byCurrent neuropharmacology · 2023Pooled it
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- COLQ-related congenital myasthenic syndrome: An integrative view.Neurogenetics · 2023Article
- Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Copy number analysis reveals a novel multiexon deletion of theNeurology. Genetics · 2016Article
- Article
- Pick one, but be quick: 5' splice sites and the problems of too many choices.Genes & development · 2013Review
- Article
- Comparative in silico analyses and experimental validation of novel splice site and missense mutations in the genes MLH1 and MSH2.Journal of cancer research and clinical oncology · 2010Article
- Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics.Genome research · 2008Article
- TAT gene mutation analysis in three Palestinian kindreds with oculocutaneous tyrosinaemia type II; characterization of a silent exonic transversion that causes complete missplicing by exon 11 skipping.Journal of inherited metabolic disease · 2006Article
- Short/branched-chain acyl-CoA dehydrogenase deficiency due to an IVS3+3A>G mutation that causes exon skipping.Human genetics · 2006Article
- Comparative analysis detects dependencies among the 5' splice-site positions.RNA (New York, N.Y.) · 2004Article
- Delineation of the mechanisms of aberrant splicing caused by two unusual intronic mutations in the RSK2 gene involved in Coffin-Lowry syndrome.Nucleic acids research · 2004Article
- Trimerization domain of the collagen tail of acetylcholinesterase.Neurochemical research · 2003Article
- Atypical 5' splice sites cause CFTR exon 9 to be vulnerable to skipping.American journal of human genetics · 2002Article
- Article
- Unusual splice-site mutations in the RSK2 gene and suggestion of genetic heterogeneity in Coffin-Lowry syndrome.American journal of human genetics · 2002Article
- Congenital myasthenic syndromes: genetic defects of the neuromuscular junction.Current neurology and neuroscience reports · 2002Review
- Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Congenital end-plate acetylcholinesterase (AChE) deficiency (CEAD), the cause of a disabling myasthenic syndrome, arises from defects in the COLQ gene, which encodes the AChE triple-helical collagenlike-tail subunit that anchors catalytic subunits of AChE to the synaptic basal lamina. Here we describe a patient with CEAD with a nonsense mutation (R315X) and a splice-donor-site mutation at position +3 of intron 16 (IVS16+3A-->G) of COLQ. Because both A and G are consensus nucleotides at the +3 position of splice-donor sites, we constructed a minigene that spans exons 15-17 and harbors IVS16+3A-->G for expression in COS cells. We found that the mutation causes skipping of exon 16. The mutant splice-donor site of intron 16 harbors five discordant nucleotides (at -3, -2, +3, +4, and +6) that do not base-pair with U1 small-nuclear RNA (snRNA), the molecule responsible for splice-donor-site recognition. Versions of the minigene harboring, at either +4 or +6, nucleotides complementary to U1 snRNA restore normal splicing. Analysis of 1,801 native splice-donor sites reveals that presence of a G nucleotide at +3 is associated with preferential usage, at positions +4 to +6, of nucleotides concordant to U1 snRNA. Analysis of 11 disease-associated IVS+3A-->G mutations indicates that, on average, two of three nucleotides at positions +4 to +6 fail to base-pair, and that the nucleotide at +4 never base-pairs, with U1 snRNA. We conclude that, with G at +3, normal splicing generally depends on the concordance that residues at +4 to +6 have with U1 snRNA, but other cis-acting elements may also be important in assuring the fidelity of splicing.
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