{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:02:01Z","timestamp":1782738121067,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,1,4]],"date-time":"2013-01-04T00:00:00Z","timestamp":1357257600000},"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":[[2013,10]]},"abstract":"Niemann\u2013Pick disease (NPD<\/jats:styled-content>) types A and B are autosomal, recessively inherited, lysosomal storage disorders caused by deficient activity of acid sphingomyelinase (E.C. 3.1.4.12) because of mutations in the sphingomyelin phosphodiesterase\u20101 (SMPD1<\/jats:styled-content><\/jats:italic>) gene. Here, we present the molecular analysis and clinical characteristics of 15 NPD<\/jats:styled-content> type A and B patients. Sequencing the SMDP1<\/jats:styled-content><\/jats:italic> gene revealed eight previously described mutations and seven novel mutations including four missense [c.682T>C (p.Cys228Arg<\/jats:styled-content>), c.1159T>C (p.Cys387Arg<\/jats:styled-content>), c.1474G>A (p.Gly492Ser<\/jats:styled-content>), and c.1795C<\/jats:styled-content>>T (p.Leu599Phe<\/jats:styled-content>)], one frameshift [c.169delG<\/jats:styled-content> (p.Ala57Leufs<\/jats:styled-content>*20)] and two splicing (c.316+1G>T and c.1341delG<\/jats:styled-content>). The most frequent mutations were p.Arg610del (21%) and p.Gly247Ser<\/jats:styled-content> (12%). Two patients homozygous for p.Arg610del and initially classified as phenotype B showed different clinical manifestations. Patients homozygous for p.Leu599Phe<\/jats:styled-content> had phenotype B, and those homozygous for c.1341delG<\/jats:styled-content> or c.316+1G>T presented phenotype A. The present results provide new insight into genotype\/phenotype correlations in NPD<\/jats:styled-content> and emphasize the difficulty of classifying patients into types A and B, supporting the idea of a continuum between these two classic phenotypes.<\/jats:p>","DOI":"10.1111\/cge.12076","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T18:31:53Z","timestamp":1355855513000},"page":"356-361","source":"Crossref","is-referenced-by-count":31,"title":["Identification of seven novel SMPD1<\/scp><\/i> mutations causing Niemann\u2013Pick disease types A and B"],"prefix":"10.1111","volume":"84","author":[{"given":"P","family":"Irun","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular Universidad de Zaragoza Zaragoza Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS) Zaragoza Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Zaragoza (U752), Barcelona (U719) Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Mall\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular Universidad de Zaragoza Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Zaragoza (U752), Barcelona (U719) Spain"},{"name":"Biochemistry and Molecular Biology Research Centre for Nanomedicine, Area T2 Nanomedicina Vall Hebron University Hospital Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Rodriguez\u2010Sureda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Zaragoza (U752), Barcelona (U719) Spain"},{"name":"Biochemistry and Molecular Biology Research Centre for Nanomedicine, Area T2 Nanomedicina Vall Hebron University Hospital Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LA","family":"Alvarez\u2010Sala","sequence":"additional","affiliation":[{"name":"Lipids Unit, Medicina Interna Gregorio Mara\u00f1\u00f3n University Hospital Madrid Spain"},{"name":"Medicine Faculty Complutense Madrid University Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Arslan","sequence":"additional","affiliation":[{"name":"Deparment of Pediatrics, Division of Pediatric Gastroenterology, Nutrition and Metabolism Dokuz Eylul University Medical Faculty Alsancak Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Bermejo","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia Hospital San Pedro de Alc\u00e1ntara, Complejo Hospitalario de C\u00e1ceres C\u00e1ceres Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Servicio de Pediatria Hospital de Alca\u00f1iz Alca\u00f1iz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Perez de Soto","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda Hospital Universitario Virgen del Roc\u00edo Sevilla Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Villal\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS) Zaragoza Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Zaragoza (U752), Barcelona (U719) Spain"},{"name":"Departamento de Hematolog\u00eda Hospital Universitario Miguel Servet Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pocovi","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular y Celular Universidad de Zaragoza Zaragoza Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IIS) Zaragoza Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER) Zaragoza (U752), Barcelona (U719) Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-5671-5"},{"issue":"13","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1016\/S0021-9258(18)93007-3","article-title":"Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full\u2010length and alternatively spliced cDNAs","volume":"266","author":"Schuchman EH","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21018"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00025.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(80)90309-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0105-y"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117084"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1612"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364015"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2003.00009.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115380"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0557-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2006.06.034"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9258"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9263"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380020414"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/gte.1997.1.13"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/345074"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-0887"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-4416-9"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12076","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12076","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T14:53:27Z","timestamp":1696344807000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,4]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1111\/cge.12076"],"URL":"https:\/\/doi.org\/10.1111\/cge.12076","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,4]]}}}