{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:15:43Z","timestamp":1790630143070,"version":"4.1.0"},"reference-count":25,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>Mutations of the <jats:italic>SPRED1<\/jats:italic> gene, one of a family of Sprouty (Spry)\/Spred proteins known to \u201cdownregulate\u201d mitogen activated protein kinase (MAPK) signalling, have been identified in patients with a mild neurofibromatosis type 1 (NF1) phenotype with pigmentary changes but no neurofibromas (Legius syndrome).To ascertain the frequency of <jats:italic>SPRED1<\/jats:italic> mutations as a cause of this phenotype and to investigate whether other <jats:italic>SPRED<\/jats:italic>\/<jats:italic>SPRY<\/jats:italic> genes may be causal, a panel of unrelated mild NF1 patients were screened for mutations of the <jats:italic>SPRED1-3<\/jats:italic> and the <jats:italic>SPRY1-4<\/jats:italic> genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>85 patients with a mild NF1 phenotype were screened for S<jats:italic>PRED1<\/jats:italic> mutations. 44 patients negative for both <jats:italic>NF1<\/jats:italic> and <jats:italic>SPRED1<\/jats:italic> mutations were then screened for <jats:italic>SPRED2-3<\/jats:italic> and <jats:italic>SPRY1-4<\/jats:italic> mutations. Complexity analysis was applied to analyse the flanking sequences surrounding the identified <jats:italic>SPRED1<\/jats:italic> mutations for the presence of direct and inverted repeats or symmetric sequence elements in order to infer probable mutational mechanism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>\n                     <jats:italic>SPRED1<\/jats:italic> mutations were identified in 6 cases; 5 were novel and included 3 nonsense (R16X, E73X, R262X), 2 frameshift (c.1048_c1049 delGG, c.149_1152del 4 bp), and a single missense mutation (V44D). Short direct or inverted repeats detected immediately adjacent to some <jats:italic>SPRED1<\/jats:italic> mutations may have led to the formation of the microdeletions and base pair substitutions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion:<\/jats:title>\n                  <jats:p>The identification of <jats:italic>SPRED1<\/jats:italic> gene mutation in NF1-like patients has major implications for counselling NF1 families.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.065474","type":"journal-article","created":{"date-parts":[[2009,5,14]],"date-time":"2009-05-14T20:26:49Z","timestamp":1242332809000},"page":"431-437","source":"Crossref","is-referenced-by-count":74,"title":["<i>SPRED1<\/i> mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype"],"prefix":"10.1136","volume":"46","author":[{"given":"G","family":"Spurlock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Chuzhanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H-Ping","family":"Jim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Side","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Haan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Kerr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Huson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Upadhyaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2009,5,13]]},"reference":[{"key":"2025101709595391000_46.7.431.1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000126500","article-title":"The neurofibromatosis: classification, clinical features and genetic counselling.","volume-title":"Neurofibromatoses","volume":"16","author":"Huson","year":"2008"},{"key":"2025101709595391000_46.7.431.2","unstructured":"Upadhyaya M Cooper DN . 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