{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T04:15:45Z","timestamp":1788754545530,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,6,13]],"date-time":"2011-06-13T00:00:00Z","timestamp":1307923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>Schlipf NA, Sch\u00fcle R, Klimpe S, Karle KN, Synofzik M, Schicks J, Riess O, Sch\u00f6ls L, Bauer P. Amplicon\u2010based high\u2010throughput pooled sequencing identifies mutations in <jats:italic>CYP7B1<\/jats:italic> and <jats:italic>SPG7<\/jats:italic> in sporadic spastic paraplegia patients.<\/jats:p><jats:p>Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder defined clinically by progressive lower limb spasticity and weakness. HSP is a genetically highly heterogeneous condition with at least 46 gene loci identified so far, involving X\u2010linked, autosomal recessive (AR) and autosomal dominant inheritance. For correct diagnosis, molecular testing is essential because clinical parameters by themselves are not reliable to differentiate HSP forms. The purpose of this study was to establish amplicon\u2010based high\u2010throughput genotyping for AR\u2010HSP. A sample of 187 index cases with apparently sporadic or recessive spastic paraplegia were analyzed by applying an array\u2010based amplification strategy. Amplicon libraries of the <jats:italic>CYP7B1<\/jats:italic>\u2013(SPG5) and <jats:italic>SPG7<\/jats:italic>\u2013gene were generated followed by a pooled next\u2010generation sequencing (NGS) approach. We identified three SPG5 and seven SPG7 patients. All had one homozygous or two heterozygous mutations. In total, 20 distinct mutations (<jats:italic>CYP<\/jats:italic>7<jats:italic>B<\/jats:italic>1<jats:italic>,n<\/jats:italic> = 4and <jats:italic>SPG<\/jats:italic>7<jats:italic>,n<\/jats:italic> = 16) including two novel <jats:italic>CYP7B1<\/jats:italic> mutations (p.G51R and p.E211KfsX3) and eight novel <jats:italic>SPG7<\/jats:italic> mutations (p.Leu8delinsLeuLeu, p.W29X, p.R139X, p.R247X, p.G344D, p.Leu346_Leu347ins11, p.R398X and p.R398Q) were detected by this comprehensive genetic testing. Our study illustrates how amplicon\u2010based NGS can be used as an efficient tool to study genotypes and mutations in large patient cohorts and complex phenotypes.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01715.x","type":"journal-article","created":{"date-parts":[[2011,5,27]],"date-time":"2011-05-27T14:56:52Z","timestamp":1306508212000},"page":"148-160","source":"Crossref","is-referenced-by-count":38,"title":["Amplicon\u2010based high\u2010throughput pooled sequencing identifies mutations in <i>CYP7B1<\/i> and <i>SPG7<\/i> in sporadic spastic paraplegia patients"],"prefix":"10.1111","volume":"80","author":[{"given":"NA","family":"Schlipf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Sch\u00fcle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Klimpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KN","family":"Karle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Synofzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Schicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Riess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Sch\u00f6ls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,13]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199708000-00006"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70258-8"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)92879-9"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e3282f190ba"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-008-0032-z"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.11.003"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2626"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03959"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-464"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-296"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.10.001"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81203-9"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000228242.53336.90"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp073"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh125"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22949"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000319700.11606.21"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20682"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.4.467"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000201185.91110.15"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21221"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.2353\/jmoldx.2010.100043"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-359"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1523"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1110"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117389"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2010.09.001"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20873"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-008-0858-y"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-009-5109-3"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-008-0158-9"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21226"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01624.x"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.10.009"}],"container-title":["Clinical 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