{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T07:37:18Z","timestamp":1708760238838},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the <jats:italic>ATP7A<\/jats:italic> gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the <jats:italic>ATP7A<\/jats:italic> gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The <jats:italic>ATP7A<\/jats:italic> gene was screened for exon duplications using multiplex ligation-dependent probe amplification (MLPA). The expression level of <jats:italic>ATP7A<\/jats:italic> was investigated by real-time PCR and detailed analysis of the <jats:italic>ATP7A<\/jats:italic> mRNA was performed by RT-PCR followed by sequencing. In order to investigate whether the identified duplicated fragments originated from a single or from two different X-chromosomes, polymorphic markers located in the duplicated fragments were analyzed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Partial <jats:italic>ATP7A<\/jats:italic> gene duplication was identified in 20 unrelated patients including one patient with Occipital Horn Syndrome (OHS). Duplications in the <jats:italic>ATP7A<\/jats:italic> gene are estimated from our material to be the disease causing mutation in 4% of the Menkes disease patients. The duplicated regions consist of between 2 and 15 exons. In at least one of the cases, the duplication was due to an intra-chromosomal event. Characterization of the <jats:italic>ATP7A<\/jats:italic> mRNA transcripts in 11 patients revealed that the duplications were organized in tandem, in a head to tail direction. The reading frame was disrupted in all 11 cases. Small amounts of wild-type transcript were found in all patients as a result of exon-skipping events occurring in the duplicated regions. In the OHS patient with a duplication of exon 3 and 4, the duplicated out-of-frame transcript coexists with an almost equally represented wild-type transcript, presumably leading to the milder phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>In general, patients with duplication of only 2 exons exhibit a milder phenotype as compared to patients with duplication of more than 2 exons. This study provides insight into exon duplications in the <jats:italic>ATP7A<\/jats:italic> gene.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1750-1172-6-73","type":"journal-article","created":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T19:20:04Z","timestamp":1323976804000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exon duplications in the ATP7A gene: Frequency and Transcriptional Behaviour"],"prefix":"10.1186","volume":"6","author":[{"given":"Mie","family":"Mogensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Skj\u00f8rringe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Silver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Horn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisbeth B","family":"M\u00f8ller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,11,10]]},"reference":[{"key":"337_CR1","first-page":"764","volume":"29","author":"H Menkes","year":"1962","unstructured":"Menkes H, Alter M, Steigleder GK, Weakley DR, Sung JH: A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. 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