{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:14:55Z","timestamp":1781709295849,"version":"3.54.5"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>GM1 gangliosidosis (GM1) is an autosomal recessive lysosomal storage disease caused by deficiency of acid beta-galactosidase (GLB1; EC3.2.1.23). Here, we identify three novel mutations in the GLB1 gene from two Han Chinese patients with GM1 that appear correlated with clinical phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>One of the two Han Chinese patients with GM1 presented with the juvenile form, and the other with the infantile form with cardiac involvement. Sequencing of the entire GLB1 gene revealed three novel mutations (p.H102 D, p.G494V, c.495_497delTCT), which were absent in 94 normal controls. Transient expression of cDNA encoding these variants was performed in COS-1 cells to evaluate \u03b2-galactosidase activities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The first case (patient 1) with the juvenile form contained two missense mutations, p.H102 D and p.A301V. Patient 2 diagnosed with the infantile form of the disease with cardiac involvement was compound heterozygous for p.G494V and c.495_497delTCT mutations. All mutant beta-galactosidases exhibited significantly reduced activity (12%, 0%, 0%, and 0% for p.H102 D, p.A301V, p.G494V, and c.495_497delTCT), compared with the wild-type beta-galactosidase cDNA clone. The mutations identified in patient 2 with cardiomyopathy were localized in the GLB1 gene region common to both lysosomal beta-galactosidase and elastin binding protein (EBP), and caused a deletion in the elastin-binding domain of EBP.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>All four mutations identified in Han Chinese patients induce significant suppression of \u03b2-galactosidase activity, correlating with severity of disease and presence of cardiomyopathy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-17-79","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T06:13:57Z","timestamp":1285827237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Three novel beta-galactosidase gene mutations in Han Chinese patients with GM1 gangliosidosis are correlated with disease severity"],"prefix":"10.1186","volume":"17","author":[{"given":"Chi-Fan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer-Yuarn","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuu-Jen","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,9,30]]},"reference":[{"key":"649_CR1","volume-title":"GM1-gangliosidosis and Morquio B disease","author":"Y Suzuki","year":"2001","unstructured":"Suzuki Y, Oshima A, Namba E: GM1-gangliosidosis and Morquio B disease. 2001, New York: McGraw-Hill, 8","edition":"8"},{"key":"649_CR2","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.ymgme.2008.04.012","volume":"94","author":"N Brunetti-Pierri","year":"2008","unstructured":"Brunetti-Pierri N, Scaglia F: GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab. 2008, 94: 391-396. 10.1016\/j.ymgme.2008.04.012.","journal-title":"Mol Genet Metab"},{"key":"649_CR3","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1089\/dna.1990.9.119","volume":"9","author":"Y Yamamoto","year":"1990","unstructured":"Yamamoto Y, Hake CA, Martin BM, Kretz KA, Ahern-Rindell AJ, Naylor SL, Mudd M, O'Brien JS: Isolation, characterization, and mapping of a human acid beta-galactosidase cDNA. DNA Cell Biol. 1990, 9: 119-127. 10.1089\/dna.1990.9.119.","journal-title":"DNA Cell Biol"},{"key":"649_CR4","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1089\/dna.1991.10.495","volume":"10","author":"H Morreau","year":"1991","unstructured":"Morreau H, Bonten E, Zhou XY, D'Azzo A: Organization of the gene encoding human lysosomal beta-galactosidase. DNA Cell Biol. 1991, 10: 495-504. 10.1089\/dna.1991.10.495.","journal-title":"DNA Cell Biol"},{"key":"649_CR5","doi-asserted-by":"crossref","first-page":"20655","DOI":"10.1016\/S0021-9258(19)47114-7","volume":"264","author":"H Morreau","year":"1989","unstructured":"Morreau H, Galjart NJ, Gillemans N, Willemsen R, van der Horst GT, d'Azzo A: Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein. J Biol Chem. 1989, 264: 20655-20663.","journal-title":"J Biol Chem"},{"key":"649_CR6","first-page":"471","volume":"377","author":"A Hinek","year":"1996","unstructured":"Hinek A: Biological roles of the non-integrin elastin\/laminin receptor. Biol Chem. 1996, 377: 471-480.","journal-title":"Biol Chem"},{"key":"649_CR7","doi-asserted-by":"publisher","first-page":"6319","DOI":"10.1074\/jbc.273.11.6319","volume":"273","author":"S Privitera","year":"1998","unstructured":"Privitera S, Prody CA, Callahan JW, Hinek A: The 67-kDa enzymatically inactive alternatively spliced variant of beta-galactosidase is identical to the elastin\/laminin-binding protein. J Biol Chem. 1998, 273: 6319-6326. 10.1074\/jbc.273.11.6319.","journal-title":"J Biol Chem"},{"key":"649_CR8","doi-asserted-by":"publisher","first-page":"4535","DOI":"10.1073\/pnas.79.15.4535","volume":"79","author":"A D'Azzo","year":"1982","unstructured":"D'Azzo A, Hoogeveen A, Reuser AJ, Robinson D, Galjaard H: Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man. Proc Natl Acad Sci USA. 1982, 79: 4535-4539. 10.1073\/pnas.79.15.4535.","journal-title":"Proc Natl Acad Sci USA"},{"key":"649_CR9","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/S0006-291X(88)80108-6","volume":"152","author":"E Nanba","year":"1988","unstructured":"Nanba E, Tsuji A, Omura K, Suzuki Y: GM1-gangliosidosis: abnormalities in biosynthesis and early processing of beta-galactosidase in fibroblasts. Biochem Biophys Res Commun. 1988, 152: 794-800. 10.1016\/S0006-291X(88)80108-6.","journal-title":"Biochem Biophys Res Commun"},{"key":"649_CR10","doi-asserted-by":"publisher","first-page":"10035","DOI":"10.1074\/jbc.275.14.10035","volume":"275","author":"A van der Spoel","year":"2000","unstructured":"van der Spoel A, Bonten E, d'Azzo A: Processing of lysosomal beta-galactosidase. The C-terminal precursor fragment is an essential domain of the mature enzyme. J Biol Chem. 2000, 275: 10035-10040. 10.1074\/jbc.275.14.10035.","journal-title":"J Biol Chem"},{"key":"649_CR11","doi-asserted-by":"crossref","first-page":"17949","DOI":"10.1016\/S0021-9258(19)37135-2","volume":"267","author":"H Morreau","year":"1992","unstructured":"Morreau H, Galjart NJ, Willemsen R, Gillemans N, Zhou XY, d'Azzo A: Human lysosomal protective protein. Glycosylation, intracellular transport, and association with beta-galactosidase in the endoplasmic reticulum. J Biol Chem. 1992, 267: 17949-17956.","journal-title":"J Biol Chem"},{"key":"649_CR12","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1101\/gad.10.24.3156","volume":"10","author":"E Bonten","year":"1996","unstructured":"Bonten E, van der Spoel A, Fornerod M, Grosveld G, d'Azzo A: Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis. Genes Dev. 1996, 10: 3156-3169. 10.1101\/gad.10.24.3156.","journal-title":"Genes Dev"},{"key":"649_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1096-4959(01)00372-4","volume":"129","author":"KE Achyuthan","year":"2001","unstructured":"Achyuthan KE, Achyuthan AM: Comparative enzymology, biochemistry and pathophysiology of human exo-alpha-sialidases (neuraminidases). Comp Biochem Physiol B Biochem Mol Biol. 2001, 129: 29-64. 10.1016\/S1096-4959(01)00372-4.","journal-title":"Comp Biochem Physiol B Biochem Mol Biol"},{"key":"649_CR14","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/humu.10268","volume":"22","author":"V Seyrantepe","year":"2003","unstructured":"Seyrantepe V, Poupetova H, Froissart R, Zabot MT, Maire I, Pshezhetsky AV: Molecular pathology of NEU1 gene in sialidosis. Hum Mutat. 2003, 22: 343-352. 10.1002\/humu.10268.","journal-title":"Hum Mutat"},{"key":"649_CR15","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1172\/JCI116280","volume":"91","author":"A Hinek","year":"1993","unstructured":"Hinek A, Rabinovitch M, Keeley F, Okamura-Oho Y, Callahan J: The 67-kD elastin\/laminin-binding protein is related to an enzymatically inactive, alternatively spliced form of beta-galactosidase. J Clin Invest. 1993, 91: 1198-1205. 10.1172\/JCI116280.","journal-title":"J Clin Invest"},{"key":"649_CR16","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L","volume":"15","author":"A Morrone","year":"2000","unstructured":"Morrone A, Bardelli T, Donati MA, Giorgi M, Di Rocco M, Gatti R, Parini R, Ricci R, Taddeucci G, D'Azzo A, Zammarchi E: beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement. Hum Mutat. 2000, 15: 354-366. 10.1002\/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L.","journal-title":"Hum Mutat"},{"key":"649_CR17","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/S0002-9440(10)64961-9","volume":"156","author":"A Hinek","year":"2000","unstructured":"Hinek A, Wilson SE: Impaired elastogenesis in Hurler disease: dermatan sulfate accumulation linked to deficiency in elastin-binding protein and elastic fiber assembly. Am J Pathol. 2000, 156: 925-938.","journal-title":"Am J Pathol"},{"key":"649_CR18","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1002\/humu.20147","volume":"25","author":"A Caciotti","year":"2005","unstructured":"Caciotti A, Donati MA, Boneh A, d'Azzo A, Federico A, Parini R, Antuzzi D, Bardelli T, Nosi D, Kimonis V: Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis. Hum Mutat. 2005, 25: 285-292. 10.1002\/humu.20147.","journal-title":"Hum Mutat"},{"key":"649_CR19","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1016\/S0002-9440(10)61251-5","volume":"167","author":"A Caciotti","year":"2005","unstructured":"Caciotti A, Donati MA, Bardelli T, d'Azzo A, Massai G, Luciani L, Zammarchi E, Morrone A: Primary and secondary elastin-binding protein defect leads to impaired elastogenesis in fibroblasts from GM1-gangliosidosis patients. Am J Pathol. 2005, 167: 1689-1698.","journal-title":"Am J Pathol"},{"key":"649_CR20","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1083\/jcb.126.2.563","volume":"126","author":"A Hinek","year":"1994","unstructured":"Hinek A, Rabinovitch M: 67-kD elastin-binding protein is a protective \"companion\" of extracellular insoluble elastin and intracellular tropoelastin. J Cell Biol. 1994, 126: 563-574. 10.1083\/jcb.126.2.563.","journal-title":"J Cell Biol"},{"key":"649_CR21","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3109\/15419069409004436","volume":"2","author":"A Hinek","year":"1994","unstructured":"Hinek A: Nature and the multiple functions of the 67-kD elastin-\/laminin binding protein. Cell Adhes Commun. 1994, 2: 185-193. 10.3109\/15419069409004436.","journal-title":"Cell Adhes Commun"},{"key":"649_CR22","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1126\/science.2832941","volume":"239","author":"A Hinek","year":"1988","unstructured":"Hinek A, Wrenn DS, Mecham RP, Barondes SH: The elastin receptor: a galactoside-binding protein. Science. 1988, 239: 1539-1541. 10.1126\/science.2832941.","journal-title":"Science"},{"key":"649_CR23","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1006\/excr.1995.1321","volume":"220","author":"A Hinek","year":"1995","unstructured":"Hinek A, Keeley FW, Callahan J: Recycling of the 67-kDa elastin binding protein in arterial myocytes is imperative for secretion of tropoelastin. Exp Cell Res. 1995, 220: 312-324. 10.1006\/excr.1995.1321.","journal-title":"Exp Cell Res"},{"key":"649_CR24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/S0079-6603(01)69045-7","volume":"69","author":"AV Pshezhetsky","year":"2001","unstructured":"Pshezhetsky AV, Ashmarina M: Lysosomal multienzyme complex: biochemistry, genetics, and molecular pathophysiology. Prog Nucleic Acid Res Mol Biol. 2001, 69: 81-114. full_text.","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"key":"649_CR25","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.1074\/jbc.M508736200","volume":"281","author":"A Hinek","year":"2006","unstructured":"Hinek A, Pshezhetsky AV, von Itzstein M, Starcher B: Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J Biol Chem. 2006, 281: 3698-3710. 10.1074\/jbc.M508736200.","journal-title":"J Biol Chem"},{"key":"649_CR26","doi-asserted-by":"publisher","first-page":"12484","DOI":"10.1074\/jbc.M609505200","volume":"282","author":"L Duca","year":"2007","unstructured":"Duca L, Blanchevoye C, Cantarelli B, Ghoneim C, Dedieu S, Delacoux F, Hornebeck W, Hinek A, Martiny L, Debelle L: The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. J Biol Chem. 2007, 282: 12484-12491. 10.1074\/jbc.M609505200.","journal-title":"J Biol Chem"},{"key":"649_CR27","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1002\/humu.21031","volume":"30","author":"D Hofer","year":"2009","unstructured":"Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H: GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hum Mutat. 2009, 30: 1214-1221. 10.1002\/humu.21031.","journal-title":"Hum Mutat"},{"issue":"3","key":"649_CR28","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1399-0004.2010.01379.x","volume":"78","author":"D Hofer","year":"2010","unstructured":"Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis B, Michelakakis H, Plecko B, Paschke E: Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations. Clin Genet. 2010, 78 (3): 236-246. 10.1111\/j.1399-0004.2010.01379.x.","journal-title":"Clin Genet"},{"key":"649_CR29","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1111\/j.1651-2227.2000.tb00398.x","volume":"89","author":"HC Lin","year":"2000","unstructured":"Lin HC, Tsai FJ, Shen WC, Tsai CH, Peng CT: Infantile form GM1 gangliosidosis with dilated cardiomyopathy: a case report. Acta Paediatr. 2000, 89: 880-883. 10.1080\/080352500750043828.","journal-title":"Acta Paediatr"},{"key":"649_CR30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1159\/000091834","volume":"61","author":"WH Pan","year":"2006","unstructured":"Pan WH, Fann CS, Wu JY, Hung YT, Ho MS, Tai TH, Chen YJ, Liao CJ, Yang ML, Cheng AT, Chen YT: Han Chinese cell and genome bank in Taiwan: purpose, design and ethical considerations. Hum Hered. 2006, 61: 27-30. 10.1159\/000091834.","journal-title":"Hum Hered"},{"key":"649_CR31","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1006\/abio.1996.0060","volume":"234","author":"M Ansaldi","year":"1996","unstructured":"Ansaldi M, Lepelletier M, Mejean V: Site-specific mutagenesis by using an accurate recombinant polymerase chain reaction method. Anal Biochem. 1996, 234: 110-111. 10.1006\/abio.1996.0060.","journal-title":"Anal Biochem"},{"issue":"Pt 3","key":"649_CR32","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1042\/bj3480621","volume":"348","author":"S Zhang","year":"2000","unstructured":"Zhang S, Bagshaw R, Hilson W, Oho Y, Hinek A, Clarke JT, Callahan JW: Characterization of beta-galactosidase mutations Asp332-- > Asn and Arg148-- > Ser, and a polymorphism, Ser532-- > Gly, in a case of GM1 gangliosidosis. Biochem J. 2000, 348 (Pt 3): 621-632. 10.1042\/0264-6021:3480621.","journal-title":"Biochem J"},{"issue":"Pt 3","key":"649_CR33","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1042\/bj2850827","volume":"285","author":"M Hubbes","year":"1992","unstructured":"Hubbes M, D'Agrosa RM, Callahan JW: Human placental beta-galactosidase. Characterization of the dimer and complex forms of the enzyme. Biochem J. 1992, 285 (Pt 3): 827-831.","journal-title":"Biochem J"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1423-0127-17-79.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T19:02:08Z","timestamp":1630609328000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/1423-0127-17-79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,30]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["649"],"URL":"https:\/\/doi.org\/10.1186\/1423-0127-17-79","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,9,30]]},"assertion":[{"value":"5 May 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"79"}}