Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus
We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site nea...
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| Veröffentlicht in: | Nature genetics 1994-10, Vol.8 (2), p.195-202 |
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| creator | Kaler, Stephen G Gallo, Linda K Proud, Virginia K Percy, Alan K Mark, Yvonne Segal, Neil A Goldstein, David S Holmes, Courtney S Gahl, William A |
| description | We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection. |
| doi_str_mv | 10.1038/ng1094-195 |
| format | Article |
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In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. 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In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. 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Gallo, Linda K ; Proud, Virginia K ; Percy, Alan K ; Mark, Yvonne ; Segal, Neil A ; Goldstein, David S ; Holmes, Courtney S ; Gahl, William A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-c44d9912c137e9e4dba312ce499aba61449fe02e64acb977f34b69cd65fcc83d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Adenosine Triphosphatases - chemistry</topic><topic>Adenosine Triphosphatases - genetics</topic><topic>Adolescent</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Cation Transport Proteins</topic><topic>Cells, Cultured</topic><topic>Ceruloplasmin - analysis</topic><topic>Copper - blood</topic><topic>Copper-transporting ATPases</topic><topic>Dihydroxyphenylalanine - blood</topic><topic>Dihydroxyphenylalanine - cerebrospinal fluid</topic><topic>DNA Mutational Analysis</topic><topic>Ehlers-Danlos Syndrome - blood</topic><topic>Ehlers-Danlos Syndrome - cerebrospinal fluid</topic><topic>Ehlers-Danlos Syndrome - classification</topic><topic>Ehlers-Danlos Syndrome - genetics</topic><topic>Exons</topic><topic>Female</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>man</topic><topic>Medical sciences</topic><topic>Menkes Kinky Hair Syndrome - blood</topic><topic>Menkes Kinky Hair Syndrome - cerebrospinal fluid</topic><topic>Menkes Kinky Hair Syndrome - genetics</topic><topic>Menkes syndrome</topic><topic>Metabolic diseases</topic><topic>Metals (hemochromatosis...)</topic><topic>Methoxyhydroxyphenylglycol - analogs & derivatives</topic><topic>Methoxyhydroxyphenylglycol - blood</topic><topic>Methoxyhydroxyphenylglycol - cerebrospinal fluid</topic><topic>Mice</topic><topic>Mice, Neurologic Mutants</topic><topic>MNK gene</topic><topic>Molecular Sequence Data</topic><topic>Occipital Bone - abnormalities</topic><topic>occipital horn syndrome</topic><topic>Other metabolic disorders</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Point Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Recombinant Fusion Proteins</topic><topic>RNA Splicing</topic><topic>Sequence Homology, Amino Acid</topic><topic>Species Specificity</topic><topic>splicing</topic><topic>Terminator Regions, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaler, Stephen G</creatorcontrib><creatorcontrib>Gallo, Linda K</creatorcontrib><creatorcontrib>Proud, Virginia K</creatorcontrib><creatorcontrib>Percy, Alan K</creatorcontrib><creatorcontrib>Mark, Yvonne</creatorcontrib><creatorcontrib>Segal, Neil A</creatorcontrib><creatorcontrib>Goldstein, David S</creatorcontrib><creatorcontrib>Holmes, Courtney S</creatorcontrib><creatorcontrib>Gahl, William A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Human Genome Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaler, Stephen G</au><au>Gallo, Linda K</au><au>Proud, Virginia K</au><au>Percy, Alan K</au><au>Mark, Yvonne</au><au>Segal, Neil A</au><au>Goldstein, David S</au><au>Holmes, Courtney S</au><au>Gahl, William A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus</atitle><jtitle>Nature genetics</jtitle><addtitle>Nat Genet</addtitle><date>1994-10-01</date><risdate>1994</risdate><volume>8</volume><issue>2</issue><spage>195</spage><epage>202</epage><pages>195-202</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>We have found mutations in the Menkes disease gene (MNK) which impair, but do not abolish, correct mRNA splicing in patients with less severe clinical phenotypes. In one family, four males aged 2-36 years with a distinctive Menkes variant have a mutation at the +3 position of a splice donor site near the 3' end of the Menkes coding sequence that is associated with exon skipping and a stable mutant transcript. In an unrelated 15-year-old male with typical occipital horn syndrome, a point mutation at the -2 exonic position of a splice donor site in the middle of the gene causes exon-skipping and activation of a cryptic splice acceptor site. In both mutations, maintenance of some normal splicing is demonstrable by RT-PCR, cDNA sequencing and ribonuclease protection.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><pmid>7842019</pmid><doi>10.1038/ng1094-195</doi><tpages>8</tpages></addata></record> |
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| ispartof | Nature genetics, 1994-10, Vol.8 (2), p.195-202 |
| issn | 1061-4036 1546-1718 |
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| subjects | Adenosine Triphosphatases - chemistry Adenosine Triphosphatases - genetics Adolescent Animals Base Sequence Biological and medical sciences Carrier Proteins - genetics Cation Transport Proteins Cells, Cultured Ceruloplasmin - analysis Copper - blood Copper-transporting ATPases Dihydroxyphenylalanine - blood Dihydroxyphenylalanine - cerebrospinal fluid DNA Mutational Analysis Ehlers-Danlos Syndrome - blood Ehlers-Danlos Syndrome - cerebrospinal fluid Ehlers-Danlos Syndrome - classification Ehlers-Danlos Syndrome - genetics Exons Female Fibroblasts - metabolism Humans Male man Medical sciences Menkes Kinky Hair Syndrome - blood Menkes Kinky Hair Syndrome - cerebrospinal fluid Menkes Kinky Hair Syndrome - genetics Menkes syndrome Metabolic diseases Metals (hemochromatosis...) Methoxyhydroxyphenylglycol - analogs & derivatives Methoxyhydroxyphenylglycol - blood Methoxyhydroxyphenylglycol - cerebrospinal fluid Mice Mice, Neurologic Mutants MNK gene Molecular Sequence Data Occipital Bone - abnormalities occipital horn syndrome Other metabolic disorders Pedigree Phenotype Point Mutation Polymerase Chain Reaction Recombinant Fusion Proteins RNA Splicing Sequence Homology, Amino Acid Species Specificity splicing Terminator Regions, Genetic |
| title | Occipital horn syndrome and a mild Menkes phenotype associated with splice site mutations at the MNK locus |
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