{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:38Z","timestamp":1753861778287,"version":"3.41.2"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gaucher disease (GD) is an autosomal recessively inherited lysosomal storage disorder caused by biallelic pathological variants in the <jats:italic>GBA1<\/jats:italic> gene. Patients present along a broad clinical spectrum, and phenotypes are often difficult to predict based on genotype alone. The variant R463C (p.Arg502Cys) exemplifies this challenge. To better characterize its different clinical presentations, we examined the records of 25 current and historical patients evaluated at the National Institutes of Health. Nine patients were classified as GD1, 14 were classified as GD3, and two had an ambiguous diagnosis between GD1 and GD3. In addition, we reviewed the published literature in PubMed and Web of Science through December 2023, identifying 62 cases with an R463C variant from 18 countries. Within the NIH cohort, the most common second variants were N370S (p.N409S) and L444P (p.L483P). R463C\/L444P was encountered in patients with GD1 and GD3 in both the NIH cohort and worldwide. In the literature, R463C\/R463C was also reported in both GD1 and GD3, although sparse phenotypic information was shared. Often the phenotype reflected what might be predicted for the second mutant allele. This diversity of phenotypes emphasizes the need for longitudinal follow\u2010up to assess symptom development and neurological involvement.<\/jats:p>","DOI":"10.1002\/ajmg.a.63630","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T13:39:20Z","timestamp":1713793160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotypic consequences of <i>GBA1<\/i> pathological variant <scp>R463C<\/scp> (p.<scp>R502C<\/scp>)"],"prefix":"10.1002","volume":"194","author":[{"given":"Emory","family":"Ryan","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2920-5315","authenticated-orcid":false,"given":"Samantha","family":"Nishimura","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grisel","family":"Lopez","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahid","family":"Tayebi","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Sidransky","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute National Institutes of Health  Bethesda USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1055\/s-0040-1720956"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_1","DOI":"10.1007\/s10038-007-0135-4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1136\/jmg.31.5.401"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1038\/jhg.2015.27"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1016\/j.bcmd.2009.02.008"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.1002\/prot.21554"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1016\/j.ymgmr.2023.101006"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1016\/j.bcmd.2005.07.005"},{"key":"e_1_2_10_10_1","first-page":"487","article-title":"Type I Gaucher's disease with homozygous R463C mutation without neurological involvement","volume":"32","author":"Bolaman Z.","year":"2002","journal-title":"Haematologia"},{"key":"e_1_2_10_11_1","first-page":"346","article-title":"Adult type 3 Gaucher disease as manifestation of R463C\/Rec Nci I mutation: First reported case in the world literature","volume":"61","author":"Chauhan V.","year":"2013","journal-title":"The Journal of the Association of Physicians of India"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1016\/j.ymgme.2021.01.002"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1186\/s13023-020-01637-9"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1016\/j.ymgmr.2021.100820"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1016\/j.ejmg.2008.02.004"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1002\/mds.26278"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1067\/S0022-3476(03)00302-0"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.1016\/j.ejim.2009.11.005"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1023\/A:1005668230365"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1136\/adc.77.1.17"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.14802\/jmd.23074"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1089\/dna.1990.9.233"},{"key":"e_1_2_10_23_1","first-page":"921","article-title":"Prevalence of nine mutations among Jewish and non\u2010Jewish Gaucher disease patients","volume":"53","author":"Horowitz M.","year":"1993","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_10_24_1","first-page":"335","article-title":"Gaucher disease type I diagnosed at 63\u2009years old presenting with thrombocytopenia","volume":"49","author":"Kawahara S.","year":"2008","journal-title":"Rinsh\u014d Ketsueki"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1016\/j.ymgme.2021.12.009"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1007\/s004390050454"},{"doi-asserted-by":"publisher","key":"e_1_2_10_27_1","DOI":"10.1093\/hmg\/ddq454"},{"doi-asserted-by":"publisher","key":"e_1_2_10_28_1","DOI":"10.1002\/ajmg.1320490212"},{"doi-asserted-by":"publisher","key":"e_1_2_10_29_1","DOI":"10.3389\/fgene.2014.00148"},{"doi-asserted-by":"publisher","key":"e_1_2_10_30_1","DOI":"10.1016\/S0065-3101(24)00142-7"},{"doi-asserted-by":"publisher","key":"e_1_2_10_31_1","DOI":"10.1002\/mds.26359"},{"doi-asserted-by":"publisher","key":"e_1_2_10_32_1","DOI":"10.1007\/BF02436006"},{"doi-asserted-by":"publisher","key":"e_1_2_10_33_1","DOI":"10.1111\/j.1399-0004.1996.tb02352.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_34_1","DOI":"10.1002\/mds.27775"},{"doi-asserted-by":"publisher","key":"e_1_2_10_35_1","DOI":"10.7124\/bc.000940"},{"doi-asserted-by":"publisher","key":"e_1_2_10_36_1","DOI":"10.1073\/pnas.1818411116"},{"doi-asserted-by":"publisher","key":"e_1_2_10_37_1","DOI":"10.1186\/s12881-019-0759-1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_38_1","DOI":"10.1016\/0140-6736(90)93424-N"},{"doi-asserted-by":"publisher","key":"e_1_2_10_39_1","DOI":"10.1136\/jnnp-2020-322857"},{"doi-asserted-by":"publisher","key":"e_1_2_10_40_1","DOI":"10.1002\/(SICI)1098\u20101004(200002)15:2<181::AID\u2010HUMU7>3.0.CO;2\u2010S"},{"doi-asserted-by":"publisher","key":"e_1_2_10_41_1","DOI":"10.1006\/bmme.1996.0021"},{"doi-asserted-by":"publisher","key":"e_1_2_10_42_1","DOI":"10.1016\/j.clinbiochem.2020.12.002"},{"doi-asserted-by":"publisher","key":"e_1_2_10_43_1","DOI":"10.1093\/qjmed\/hcw002"},{"doi-asserted-by":"publisher","key":"e_1_2_10_44_1","DOI":"10.1006\/bcmd.2001.0410"},{"doi-asserted-by":"publisher","key":"e_1_2_10_45_1","DOI":"10.1097\/01.gim.0000196443.42899.25"},{"key":"e_1_2_10_46_1","first-page":"316","article-title":"Clinical and molecular aspects of Gaucher disease in New Zealand","volume":"110","author":"Woodfield M. J.","year":"1997","journal-title":"The New Zealand Medical Journal"},{"key":"e_1_2_10_47_1","first-page":"82","article-title":"Gaucher disease type 1, incidentally found on a periodic physical examination","volume":"37","author":"Yoshida K.","year":"1996","journal-title":"Rinsh\u014d Ketsueki"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T15:24:45Z","timestamp":1728487485000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":46,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/ajmg.a.63630"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63630","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2024,4,22]]},"assertion":[{"value":"2024-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63630"}}