ArticleAmerican journal of human genetics2000
Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome.
Article in American journal of human genetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 127 citations in OpenAlex.
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- Novel genes and variants associated with congenital pituitary hormone deficiency in the era of next-generation sequencing.Frontiers in endocrinology · 2022Review
- Identification of a Novel Deep Intronic Variant by Whole Genome Sequencing Combined With RNA Sequencing in a Chinese Patient With Menkes Disease.Frontiers in genetics · 2022Article
- Occipital Horn Syndrome as a Result of Splice Site Mutations inFrontiers in molecular neuroscience · 2021Article
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- A Bioinformatics-Based Alternative mRNA Splicing Code that May Explain Some Disease Mutations Is Conserved in Animals.Frontiers in genetics · 2017Article
- Abdominal aortic aneurysm in a patient with occipital horn syndrome.Journal of vascular surgery cases · 2015Article
- Mottled Mice and Non-Mammalian Models of Menkes Disease.Frontiers in molecular neuroscience · 2015Review
- Functional characterization of the spf/ash splicing variation in OTC deficiency of mice and man.PloS one · 2015Article
- Occipital horn syndrome and classical Menkes Syndrome caused by deep intronic mutations, leading to the activation of ATP7A pseudo-exon.European journal of human genetics : EJHG · 2014Article
- ATP7B variants as modulators of copper dyshomeostasis in Alzheimer's disease.Neuromolecular medicine · 2013Article
- Copper phenotype in Alzheimer's disease: dissecting the pathway.American journal of neurodegenerative disease · 2013Article
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
More than 150 point mutations have now been identified in the ATP7A gene. Most of these mutations lead to the classic form of Menkes disease (MD), and a few lead to the milder occipital horn syndrome (OHS). To get a better understanding of molecular changes leading to classic MD and OHS, we took advantage of the unique finding of three patients with similar mutations but different phenotypes. Although all three patients had mutations located in the splice-donor site of intron 6, only two of the patients had the MD phenotype; the third had the OHS phenotype. Fibroblast cultures from the three patients were analyzed by reverse transcriptase (RT)-PCR to try to find an explanation of the different phenotypes. In all three patients, exon 6 was deleted in the majority of the ATP7A transcripts. However, by RT-PCR amplification with an exon 6-specific primer, we were able to amplify exon 6-containing mRNA products from all three patients, even though they were in low abundance. Sequencing of these products indicated that only the patient with OHS had correctly spliced exon 6-containing transcripts. We used two different methods of quantitative RT-PCR analysis and found that the level of correctly spliced mRNA in this patient was 2%-5% of the level found in unaffected individuals. These findings indicate that the presence of barely detectable amounts of correctly spliced ATP7A transcript is sufficient to permit the development of the milder OHS phenotype, as opposed to classic MD.
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