Molecular and biochemical characterization of a novel intronic single point mutation in a Tunisian family with glycogen storage disease type III
详细信息 查看全文
- 作者：Faten Ben Rhouma (1) (2) (7)
Hatem Azzouz (2) (3)
Fran?ois M. Petit (4)
Mariem Ben Khelifa (1) (7)
Amel Ben Chehida (2) (3)
Fehmi Nasrallah (5)
Frédéric Parisot (4)
Khaled Lasram (1) (7)
Rym Kefi (1) (7)
Yosra Bouyacoub (1) (7)
Lilia Romdhane (1) (8)
Christiane Baussan (6)
Naziha Kaabachi (2) (5)
Marie-Fran?oise Ben Dridi (2) (3)
Neji Tebib (2) (3)
Sonia Abdelhak (1) (7) (9) - 关键词：Glycogenosis type III ; Novel mutation ; AGL gene ; RT ; PCR ; Tunisian patients ; Aberrant splicing
- 刊名：Molecular Biology Reports
- 出版年：2013
- 出版时间：July 2013
- 年：2013
- 卷：40
- 期：7
- 页码：4197-4202
- 全文大小：296KB
- 参考文献：1. Shen JJ, Chen YT (2002) Molecular characterization of glycogen storage disease type III. Curr Mol Med 2(2):167-75 CrossRef
2. Shen JJ, Bao Y, Liu HM, Lee P, Leonard JV, Chen YT (1996) Mutations in exon 3 of the glycogen debranching enzyme gene are associated with glycogen storage disease type III that is differentially expressed in liver and muscle. J Clin Invest 98(2):352-57 CrossRef
3. Van Hoof F, Hers HG (1967) The subgroups of type 3 glycogenosis. Eur J Biochem 2:265-70 CrossRef
4. Lucchiari S, Pagliarani S, Salani S, Filocamo M, Di Rocco M, Melis D, Rodolico C, Musumeci O, Toscano A, Bresolin N, Comi GP (2006) Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. Hum Mutat 27(6):600-01. doi:10.1002/humu.9426 CrossRef
5. Okubo M, Horinishi A, Nakamura N, Aoyama Y, Hashimoto M, Endo Y, Murase T (1998) A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12-gt;G) but no exon 3 mutations in the glycogen debranching enzyme gene in a homozygous patient with glycogen storage disease type IIIb. Hum Genet 102(1):1- CrossRef
6. Yang BZ, Ding JH, Enghild JJ, Bao Y, Chen YT (1992) Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen debranching enzyme. J Biol Chem 267(13):9294-299
7. Parvari R, Moses S, Shen J, Hershkovitz E, Lerner A, Chen YT (1997) A single-base deletion in the 3-coding region of glycogen-debranching enzyme is prevalent in glycogen storage disease type IIIA in a population of North African Jewish patients. Eur J Hum Genet 5(5):266-70
8. Santer R, Kinner M, Steuerwald U, Kjaergaard S, Skovby F, Simonsen H, Shaiu WL, Chen YT, Schneppenheim R, Schaub J (2001) Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands. Eur J Hum Genet 9(5):388-91. doi:10.1038/sj.ejhg.5200632 CrossRef
9. Aoyama Y, Ozer I, Demirkol M, Ebara T, Murase T, Podskarbi T, Shin YS, Gokcay G, Okubo M (2009) Molecular features of 23 patients with glycogen storage disease type III in Turkey: a novel mutation p.R1147G associated with isolated glucosidase deficiency, along with 9 AGL mutations. J Hum Genet 54(11):681-86. doi:10.1038/jhg.2009.100 CrossRef
10. Okubo M, Aoyama Y, Murase T (1996) A novel donor splice site mutation in the glycogen debranching enzyme gene is associated with glycogen storage disease type III (vol 224, pg 493, 1996). Biochem Biophys Res Commun 225(2):695 CrossRef
11. Okubo M, Horinishi A, Suzuki Y, Murase T, Hayasaka K (2000) Compound heterozygous patient with glycogen storage disease type III: identification of two novel AGL mutations, a donor splice site mutation of Chinese origin and a 1-bp deletion of Japanese origin. Am J Med Genet 93(3):211-14 CrossRef
12. Okubo M, Horinishi A, Takeuchi M, Suzuki Y, Sakura N, Hasegawa Y, Igarashi T, Goto K, Tahara H, Uchimoto S, Omichi K, Kanno H, Hayasaka K, Murase T (2000) Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan. Hum Genet 106(1):108-15 CrossRef
13. Shen JJ, Bao Y, Chen YT (1997) A nonsense mutation due to a single base insertion in the 3-coding region of glycogen debranching enzyme gene associated with a severe phenotype in a patient with glycogen storage disease type IIIa. Hum Mutat 9(1):37-0 CrossRef
14. Endo Y, Horinishi A, Vorgerd M, Aoyama Y, Ebara T, Murase T, Odawara M, Podskarbi T, Shin YS, Okubo M (2006) Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey. J Hum Genet 51(11):958-63. doi:10.1007/s10038-006-0045-x CrossRef
15. Lucchiari S, Fogh I, Prelle A, Parini R, Bresolin N, Melis D, Fiori L, Scarlato G, Comi GP (2002) Clinical and genetic variability of glycogen storage disease type IIIa: seven novel / AGL gene mutations in the Mediterranean area. Am J Med Genet 109(3):183-90. doi:10.1002/ajmg.10347 CrossRef
16. Horinishi A, Okubo M, Tang NL, Hui J, To KF, Mabuchi T, Okada T, Mabuchi H, Murase T (2002) Mutational and haplotype analysis of AGL in patients with glycogen storage disease type III. J Hum Genet 47(2):55-9. doi:10.1007/s100380200000 CrossRef
17. Maire I, Baussan C, Moatti N, Mathieu M, Lemonnier A (1991) Biochemical diagnosis of hepatic glycogen storage diseases: 20?years French experience. Clin Biochem 24(2):169-78 CrossRef
18. Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C (2009) Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37(9):e67. doi:10.1093/nar/gkp215 CrossRef
19. Reese MG, Eeckman FH, Kulp D, Haussler D (1997) Improved splice site detection in Genie. J Comput Biol 4(3):311-23 CrossRef
20. Blanco E, Parra G, Guigó R (2007) Using geneid to identify genes. Curr Protoc Bioinformatics 4(4.3):1-8
21. Yeo G, Burge CB (2004) Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. J Comput Biol 11(2-):377-94 CrossRef
22. Momoi T, Sano H, Yamanaka C, Sasaki H, Mikawa H (1992) Glycogen storage disease type III with muscle involvement: reappraisal of phenotypic variability and prognosis. Am J Med Genet 42(5):696-99. doi:10.1002/ajmg.1320420514 CrossRef
23. Lee P, Burch M, Leonard JV (1995) Plasma creatine kinase and cardiomyopathy in glycogen storage disease type III. J Inherit Metab Dis 18(6):751-52 CrossRef
24. Coleman RA, Winter HS, Wolf B, Gilchrist JM, Chen YT (1992) Glycogen storage disease type III (glycogen debranching enzyme deficiency): correlation of biochemical defects with myopathy and cardiomyopathy. Ann Intern Med 116(11):896-00 CrossRef
25. Baralle D, Baralle M (2005) Splicing in action: assessing disease causing sequence changes. J Med Genet 42(10):737-48. doi:10.1136/jmg.2004.029538 CrossRef
26. Krawczak M, Reiss J, Cooper DN (1992) The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. Hum Genet 90(1-):41-4
27. Crispino JD, Mermoud JE, Lamond AI, Sharp PA (1996) Cis-acting elements distinct from the 5-splice site promote U1-independent pre-mRNA splicing. RNA 2(7):664-73
28. Hadjigeorgiou GM, Comi GP, Bordoni A, Shen J, Chen YT, Salani S, Toscano A, Fortunato F, Lucchiari S, Bresolin N, Rodolico C, Piscaglia MG, Franceschina L, Papadimitriou A, Scarlato G (1999) Novel donor splice site mutations of AGL gene in glycogen storage disease type IIIa. J Inherit Metab Dis 22(6):762-63 CrossRef
29. Lucchiari S, Donati MA, Melis D, Filocamo M, Parini R, Bresolin N, Comi GP (2003) Mutational analysis of the AGL gene: five novel mutations in GSD III patients. Hum Mutat 22(4):337. doi:10.1002/humu.9177 CrossRef
30. Mili A, Ben Charfeddine I, Amara A, Mamai O, Adala L, Ben Lazreg T, Bouguila J, Saad A, Limem K, Gribaa M (2012) A c.3216_3217delGA mutation in AGL gene in Tunisian patients with a glycogen storage disease type III: evidence of a founder effect. Clin Genet 82(6):534-39. doi:10.1111/j.1399-0004.2011.01806.x CrossRef
31. Mili A, Ben Charfeddine I, Mamai O, Abdelhak S, Adala L, Amara A, Pagliarani S, Lucchiarri S, Ayadi A, Tebib N, Harbi A, Bouguila J, H’Mida D, Saad A, Limem K, Comi GP, Gribaa M (2012) Molecular and biochemical characterization of Tunisian patients with glycogen storage disease type III. J Hum Genet 57(3):170-75. doi:10.1038/jhg.2011.122 CrossRef
32. Cherif W, Ben Rhouma F, Messai H, Mili A, Gribaa M, Kefi R, Ayadi A, Boughamoura L, Chemli J, Saad A, Kaabachi N, Sfar MT, Ben Dridi MF, Tebib N, Abdelhak S (2012) High frequency of W1327X mutation in glycogen storage disease type III patients from central Tunisia. Ann Biol Clin (Paris) 70(6):648-50. doi:10.1684/abc.2012.0766 - 作者单位：Faten Ben Rhouma (1) (2) (7)
Hatem Azzouz (2) (3)
Fran?ois M. Petit (4)
Mariem Ben Khelifa (1) (7)
Amel Ben Chehida (2) (3)
Fehmi Nasrallah (5)
Frédéric Parisot (4)
Khaled Lasram (1) (7)
Rym Kefi (1) (7)
Yosra Bouyacoub (1) (7)
Lilia Romdhane (1) (8)
Christiane Baussan (6)
Naziha Kaabachi (2) (5)
Marie-Fran?oise Ben Dridi (2) (3)
Neji Tebib (2) (3)
Sonia Abdelhak (1) (7) (9)
1. Laboratoire de Genomique Biomedicale et Oncogenetique LR11IPT05, Institut Pasteur de Tunis, 1002, Tunis, Tunisia
2. Faculté de Médecine de Tunis, Unité des Maladies Neurologiques de l’Enfant, 1007, Tunis, Tunisia
7. Université Tunis El Manar, 1068, Tunis, Tunisia
3. H?pital La Rabta de Tunis, Département de Pédiatrie, Unité des maladies métaboliques héréditaires, 1007, Tunis, Tunisia
4. AP-HP, Laboratoire de Génétique Moléculaire, H?pital Antoine Béclère, 92141, Clamart, France
5. Laboratoire de Biochimie, H?pital La Rabta de Tunis, 1007, Tunis, Tunisia
8. Université de Carthage, 1054, Tunis, Tunisia
6. Laboratoire de Biochimie, H?pital Bicêtre, 78 rue du Général Leclerc, 94275, Le Kremlin Bicêtre, France
9. Biomedical Genomics and Oncogenetic Laboratory, Pasteur Institute of Tunis, BP74, 13 Place Pasteur, 1002, Tunis, Belvédère, Tunisia - ISSN：1573-4978
文摘
Genetic deficiency of the glycogen debranching enzyme causes glycogen storage disease type III, an autosomal recessive inherited disorder. The gene encoding this enzyme is designated as AGL gene. The disease is characterized by fasting hypoglycemia, hepatomegaly, growth retardation, progressive myopathy and cardiomyopathy. In the present study, we present clinical features and molecular characterization of two consanguineous Tunisian siblings suffering from Glycogen storage disease type III. The full coding exons of the AGL gene and their corresponding exon–intron boundaries were amplified for the patients and their parents. Gene sequencing identified a novel single point mutation at the conserved polypyrimidine tract of intron 21 in a homozygous state (IVS21-8A>G). This variant cosegregated with the disease and was absent in 102 control chromosomes. In silico analysis using online resources showed a decreased score of the acceptor splice site of intron 21. RT-PCR analysis of the AGL splicing pattern revealed a 7?bp sequence insertion between exon 21 and exon 22 due to the creation of a new 3-splice site. The predicted mutant enzyme was truncated by the loss of 637 carboxyl-terminal amino acids as a result of premature termination. This novel mutation is the first mutation identified in the region of Bizerte and the tenth AGL mutation identified in Tunisia. Screening for this mutation can improve the genetic counseling and prenatal diagnosis of GSD III.