{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:28:11Z","timestamp":1791260891320,"version":"4.1.0"},"reference-count":66,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2010,3,6]]},"published-print":{"date-parts":[[2010,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Large deletions of the <jats:italic>NF1<\/jats:italic> gene region occur in \u223c5% of patients with neurofibromatosis type-1 (NF1) and are associated with particularly severe manifestations of the disease. However, until now, the genotype\u2013phenotype relationship has not been comprehensively studied in patients harbouring large <jats:italic>NF1<\/jats:italic> gene deletions of comparable extent (giving rise to haploinsufficiency of the same genes).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Method<\/jats:title>\n                  <jats:p>We have performed the most comprehensive clinical\/neuropsychological characterisation so far undertaken in <jats:italic>NF1<\/jats:italic> deletion patients, involving 29 patients with precisely determined type-1 <jats:italic>NF1<\/jats:italic> (1.4\u2005Mb) deletions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Novel clinical features found to be associated with type-1 <jats:italic>NF1<\/jats:italic> deletions included pes cavus (17% of patients), bone cysts (50%), attention deficit (73%), muscular hypotonia (45%) and speech difficulties (48%). Type-1 <jats:italic>NF1<\/jats:italic> deletions were found to be disproportionately associated with facial dysmorphic features (90% of patients), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and\/or learning disabilities (93%) and mental retardation (IQ&lt;70; 38%), as compared with the general NF1 patient population. Significantly increased frequencies (relative to the general NF1 population) of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and MPNSTs (21%) were also noted in the type-1 deletion patients. Further, 50% of the adult patients exhibited a very high burden of cutaneous neurofibromas (N\u22651000).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings emphasise the importance of deletion analysis in NF1 since frequent monitoring of tumour presence and growth could potentiate early surgical intervention thereby improving patient survival.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2009.075937","type":"journal-article","created":{"date-parts":[[2010,6,12]],"date-time":"2010-06-12T20:14:09Z","timestamp":1276373649000},"page":"623-630","source":"Crossref","is-referenced-by-count":156,"title":["Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4\u2005Mb type-1 <i>NF1<\/i> deletions"],"prefix":"10.1136","volume":"47","author":[{"given":"V-F","family":"Mautner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Kluwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R E","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A C","family":"Roehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Bammert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"H\u00f6gel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Sp\u00f6ri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D N","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kehrer-Sawatzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2010,6,12]]},"reference":[{"key":"2025101713553820000_47.9.623.1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10299"},{"key":"2025101713553820000_47.9.623.2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.1.35"},{"key":"2025101713553820000_47.9.623.3","doi-asserted-by":"publisher","DOI":"10.1086\/323043"},{"key":"2025101713553820000_47.9.623.4","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.13.1387"},{"key":"2025101713553820000_47.9.623.5","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20065"},{"key":"2025101713553820000_47.9.623.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng1920"},{"key":"2025101713553820000_47.9.623.7","doi-asserted-by":"publisher","DOI":"10.1086\/423624"},{"key":"2025101713553820000_47.9.623.8","doi-asserted-by":"publisher","DOI":"10.1086\/522089"},{"key":"2025101713553820000_47.9.623.9","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.059329"},{"key":"2025101713553820000_47.9.623.10","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.033795"},{"key":"2025101713553820000_47.9.623.11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/ajmg.a.32045","article-title":"Absence of cutaneous neurofibromas in an NF1 patient with an atypical deletion partially overlapping the common 1.4 Mb microdeleted region","volume":"146A","author":"Kehrer-Sawatzki","year":"2008","journal-title":"Am J Med Genet A"},{"key":"2025101713553820000_47.9.623.12","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2009.090064"},{"key":"2025101713553820000_47.9.623.13","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.014761"},{"key":"2025101713553820000_47.9.623.14","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.034256"},{"key":"2025101713553820000_47.9.623.15","doi-asserted-by":"publisher","DOI":"10.1086\/374821"},{"key":"2025101713553820000_47.9.623.16","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/ajmg.a.30346","article-title":"Intelligence in individuals with a neurofibromatosis type 1 microdeletion","volume":"131","author":"Descheemaeker","year":"2004","journal-title":"Am J Med Genet A"},{"key":"2025101713553820000_47.9.623.17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201419"},{"key":"2025101713553820000_47.9.623.18","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971128)73:1<80::AID-AJMG16>3.0.CO;2-N"},{"key":"2025101713553820000_47.9.623.19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/gcc.20289","article-title":"Spectrum of single- and multiexon NF1 copy number changes in a cohort of 1,100 unselected NF1 patients","volume":"5","author":"Wimmer","year":"2006","journal-title":"Genes Chromosomes Cancer"},{"key":"2025101713553820000_47.9.623.20","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.053785"},{"key":"2025101713553820000_47.9.623.21","unstructured":"Riccardi VM . 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