3wez

Structural highlights

Disease

[BGAL_HUMAN] GM1 gangliosidosis type 2;Mucopolysaccharidosis type 4B;GM1 gangliosidosis type 1;GM1 gangliosidosis type 3. GM1-gangliosidosis 1 (GM1G1) [MIM:230500]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1-gangliosidosis type 1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]} GM1-gangliosidosis 2 (GM1G2) [MIM:230600]: A gangliosidosis characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[18] [19] [20] [21] [22] [23] [24] [25] [26]} GM1-gangliosidosis 3 (GM1G3) [MIM:230650]: A gangliosidosis with a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[27] [28] [29] [30] [31] [32] [33] [34] [35] [36]} Mucopolysaccharidosis 4B (MPS4B) [MIM:253010]: A form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[37] [38] [39] [40] [41] [42] [43]}

Function

[BGAL_HUMAN] Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.^[44] Isoform 2 has no beta-galactosidase catalytic activity, but plays functional roles in the formation of extracellular elastic fibers (elastogenesis) and in the development of connective tissue. Seems to be identical to the elastin-binding protein (EBP), a major component of the non-integrin cell surface receptor expressed on fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and certain cancer cell types. In elastin producing cells, associates with tropoelastin intracellularly and functions as a recycling molecular chaperone which facilitates the secretions of tropoelastin and its assembly into elastic fibers.^[45]

References

1. ↑ Oshima A, Yoshida K, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y. Human beta-galactosidase gene mutations in morquio B disease. Am J Hum Genet. 1991 Nov;49(5):1091-3. PMID:1928092
2. ↑ Nishimoto J, Nanba E, Inui K, Okada S, Suzuki K. GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. Am J Hum Genet. 1991 Sep;49(3):566-74. PMID:1909089
3. ↑ Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y. Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. Am J Hum Genet. 1991 Aug;49(2):435-42. PMID:1907800
4. ↑ Mosna G, Fattore S, Tubiello G, Brocca S, Trubia M, Gianazza E, Gatti R, Danesino C, Minelli A, Piantanida M. A homozygous missense arginine to histidine substitution at position 482 of the beta-galactosidase in an Italian infantile GM1-gangliosidosis patient. Hum Genet. 1992 Nov;90(3):247-50. PMID:1487238
5. ↑ Boustany RM, Qian WH, Suzuki K. Mutations in acid beta-galactosidase cause GM1-gangliosidosis in American patients. Am J Hum Genet. 1993 Oct;53(4):881-8. PMID:8213816
6. ↑ Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, Kleijer W, Levade T, Michelakakis H, Radeva B. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet. 2001 Aug;109(2):159-66. PMID:11511921
7. ↑ Bagshaw RD, Zhang S, Hinek A, Skomorowski MA, Whelan D, Clarke JT, Callahan JW. Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease. Biochim Biophys Acta. 2002 Dec 12;1588(3):247-53. PMID:12393180
8. ↑ Silva CM, Severini MH, Sopelsa A, Coelho JC, Zaha A, d'Azzo A, Giugliani R. Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis. Hum Mutat. 1999;13(5):401-9. PMID:10338095 doi:<401::AID-HUMU9>3.0.CO;2-N 10.1002/(SICI)1098-1004(1999)13:5<401::AID-HUMU9>3.0.CO;2-N
9. ↑ 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 Jun 15;348 Pt 3:621-32. PMID:10839995
10. ↑ 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(4):354-66. PMID:10737981 doi:<354::AID-HUMU8>3.0.CO;2-L 10.1002/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L
11. ↑ Georgiou T, Drousiotou A, Campos Y, Caciotti A, Sztriha L, Gururaj A, Ozand P, Zammarchi E, Morrone A, D'Azzo A. Four novel mutations in patients from the Middle East with the infantile form of GM1-gangliosidosis. Hum Mutat. 2004 Oct;24(4):352. PMID:15365997 doi:10.1002/humu.9279
12. ↑ Caciotti A, Donati MA, Boneh A, d'Azzo A, Federico A, Parini R, Antuzzi D, Bardelli T, Nosi D, Kimonis V, Zammarchi E, Morrone A. Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis. Hum Mutat. 2005 Mar;25(3):285-92. PMID:15714521 doi:10.1002/humu.20147
13. ↑ Gururaj A, Sztriha L, Hertecant J, Johansen JG, Georgiou T, Campos Y, Drousiotou A, d'Azzo A. Magnetic resonance imaging findings and novel mutations in GM1 gangliosidosis. J Child Neurol. 2005 Jan;20(1):57-60. PMID:15791924
14. ↑ Santamaria R, Chabas A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct;27(10):1060. PMID:16941474 doi:10.1002/humu.9451
15. ↑ Tatano Y, Takeuchi N, Kuwahara J, Sakuraba H, Takahashi T, Takada G, Itoh K. Elastogenesis in cultured dermal fibroblasts from patients with lysosomal beta-galactosidase, protective protein/cathepsin A and neuraminidase-1 deficiencies. J Med Invest. 2006 Feb;53(1-2):103-12. PMID:16538002
16. ↑ Santamaria R, Blanco M, Chabas A, Grinberg D, Vilageliu L. Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. Clin Genet. 2007 Mar;71(3):273-9. PMID:17309651 doi:CGE767
17. ↑ Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H, Radeva B, Ramaswami U, Plecko B, Paschke E. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hum Mutat. 2009 Aug;30(8):1214-21. doi: 10.1002/humu.21031. PMID:19472408 doi:10.1002/humu.21031
18. ↑ Nishimoto J, Nanba E, Inui K, Okada S, Suzuki K. GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. Am J Hum Genet. 1991 Sep;49(3):566-74. PMID:1909089
19. ↑ Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y. Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. Am J Hum Genet. 1991 Aug;49(2):435-42. PMID:1907800
20. ↑ Boustany RM, Qian WH, Suzuki K. Mutations in acid beta-galactosidase cause GM1-gangliosidosis in American patients. Am J Hum Genet. 1993 Oct;53(4):881-8. PMID:8213816
21. ↑ 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(4):354-66. PMID:10737981 doi:<354::AID-HUMU8>3.0.CO;2-L 10.1002/(SICI)1098-1004(200004)15:4<354::AID-HUMU8>3.0.CO;2-L
22. ↑ Caciotti A, Donati MA, Boneh A, d'Azzo A, Federico A, Parini R, Antuzzi D, Bardelli T, Nosi D, Kimonis V, Zammarchi E, Morrone A. Role of beta-galactosidase and elastin binding protein in lysosomal and nonlysosomal complexes of patients with GM1-gangliosidosis. Hum Mutat. 2005 Mar;25(3):285-92. PMID:15714521 doi:10.1002/humu.20147
23. ↑ Santamaria R, Chabas A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct;27(10):1060. PMID:16941474 doi:10.1002/humu.9451
24. ↑ Santamaria R, Blanco M, Chabas A, Grinberg D, Vilageliu L. Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. Clin Genet. 2007 Mar;71(3):273-9. PMID:17309651 doi:CGE767
25. ↑ Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H, Radeva B, Ramaswami U, Plecko B, Paschke E. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hum Mutat. 2009 Aug;30(8):1214-21. doi: 10.1002/humu.21031. PMID:19472408 doi:10.1002/humu.21031
26. ↑ Caciotti A, Bardelli T, Cunningham J, D'Azzo A, Zammarchi E, Morrone A. Modulating action of the new polymorphism L436F detected in the GLB1 gene of a type-II GM1 gangliosidosis patient. Hum Genet. 2003 Jul;113(1):44-50. Epub 2003 Mar 19. PMID:12644936 doi:10.1007/s00439-003-0930-8
27. ↑ Nishimoto J, Nanba E, Inui K, Okada S, Suzuki K. GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification of four mutations in different clinical phenotypes among Japanese patients. Am J Hum Genet. 1991 Sep;49(3):566-74. PMID:1909089
28. ↑ Yoshida K, Oshima A, Shimmoto M, Fukuhara Y, Sakuraba H, Yanagisawa N, Suzuki Y. Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common mutation among Japanese adult/chronic cases. Am J Hum Genet. 1991 Aug;49(2):435-42. PMID:1907800
29. ↑ Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, Kleijer W, Levade T, Michelakakis H, Radeva B. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet. 2001 Aug;109(2):159-66. PMID:11511921
30. ↑ Santamaria R, Chabas A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct;27(10):1060. PMID:16941474 doi:10.1002/humu.9451
31. ↑ Santamaria R, Blanco M, Chabas A, Grinberg D, Vilageliu L. Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. Clin Genet. 2007 Mar;71(3):273-9. PMID:17309651 doi:CGE767
32. ↑ Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H, Radeva B, Ramaswami U, Plecko B, Paschke E. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hum Mutat. 2009 Aug;30(8):1214-21. doi: 10.1002/humu.21031. PMID:19472408 doi:10.1002/humu.21031
33. ↑ Chakraborty S, Rafi MA, Wenger DA. Mutations in the lysosomal beta-galactosidase gene that cause the adult form of GM1 gangliosidosis. Am J Hum Genet. 1994 Jun;54(6):1004-13. PMID:8198123
34. ↑ Ishii N, Oohira T, Oshima A, Sakuraba H, Endo F, Matsuda I, Sukegawa K, Orii T, Suzuki Y. Clinical and molecular analysis of a Japanese boy with Morquio B disease. Clin Genet. 1995 Aug;48(2):103-8. PMID:7586649
35. ↑ Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, Kleijer W, Levade T, Michelakakis H, Radeva B. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet. 2001 Aug;109(2):159-66. PMID:11511921
36. ↑ Roze E, Paschke E, Lopez N, Eck T, Yoshida K, Maurel-Ollivier A, Doummar D, Caillaud C, Galanaud D, Billette de Villemeur T, Vidailhet M, Roubergue A. Dystonia and parkinsonism in GM1 type 3 gangliosidosis. Mov Disord. 2005 Oct;20(10):1366-9. PMID:15986423 doi:10.1002/mds.20593
37. ↑ Oshima A, Yoshida K, Shimmoto M, Fukuhara Y, Sakuraba H, Suzuki Y. Human beta-galactosidase gene mutations in morquio B disease. Am J Hum Genet. 1991 Nov;49(5):1091-3. PMID:1928092
38. ↑ Santamaria R, Chabas A, Coll MJ, Miranda CS, Vilageliu L, Grinberg D. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct;27(10):1060. PMID:16941474 doi:10.1002/humu.9451
39. ↑ Tatano Y, Takeuchi N, Kuwahara J, Sakuraba H, Takahashi T, Takada G, Itoh K. Elastogenesis in cultured dermal fibroblasts from patients with lysosomal beta-galactosidase, protective protein/cathepsin A and neuraminidase-1 deficiencies. J Med Invest. 2006 Feb;53(1-2):103-12. PMID:16538002
40. ↑ Hofer D, Paul K, Fantur K, Beck M, Burger F, Caillaud C, Fumic K, Ledvinova J, Lugowska A, Michelakakis H, Radeva B, Ramaswami U, Plecko B, Paschke E. GM1 gangliosidosis and Morquio B disease: expression analysis of missense mutations affecting the catalytic site of acid beta-galactosidase. Hum Mutat. 2009 Aug;30(8):1214-21. doi: 10.1002/humu.21031. PMID:19472408 doi:10.1002/humu.21031
41. ↑ Paschke E, Milos I, Kreimer-Erlacher H, Hoefler G, Beck M, Hoeltzenbein M, Kleijer W, Levade T, Michelakakis H, Radeva B. Mutation analyses in 17 patients with deficiency in acid beta-galactosidase: three novel point mutations and high correlation of mutation W273L with Morquio disease type B. Hum Genet. 2001 Aug;109(2):159-66. PMID:11511921
42. ↑ Ishii N, Oohira T, Oshima A, Sakuraba H, Endo F, Matsuda I, Sukegawa K, Orii T, Suzuki Y. Clinical and molecular analysis of a Japanese boy with Morquio B disease. Clin Genet. 1995 Aug;48(2):103-8. PMID:7586649
43. ↑ Bagshaw RD, Zhang S, Hinek A, Skomorowski MA, Whelan D, Clarke JT, Callahan JW. Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease. Biochim Biophys Acta. 2002 Dec 12;1588(3):247-53. PMID:12393180
44. ↑ Hinek A. Biological roles of the non-integrin elastin/laminin receptor. Biol Chem. 1996 Jul-Aug;377(7-8):471-80. PMID:8922281
45. ↑ Hinek A. Biological roles of the non-integrin elastin/laminin receptor. Biol Chem. 1996 Jul-Aug;377(7-8):471-80. PMID:8922281