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Yuan-tsong Chen - One of the best experts on this subject based on the ideXlab platform.
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Glycogen Debranching Enzyme is associated with rat skeletal muscle sarcoplasmic reticulum.
Acta physiologica Scandinavica, 2004Co-Authors: S. J. Lees, Yuan-tsong Chen, J. H. WilliamsAbstract:AIMS: Gel electrophoresis revealed a band of molecular weight approximately 160 000 Da associated with the skeletal muscle sarcoplasmic reticulum (SR) vesicle preparations. This investigation sought to examine Glycogen Debranching Enzyme associated with skeletal muscle SR. METHODS: Sarcoplasmic reticulum samples were also taken from muscle whose Glycogen content had been reduced either via stimulation of the sciatic nerve or alpha-amylase treatment of muscle homogenates. RESULTS: The stimulation protocol reduced whole muscle Glycogen by 86% (7.4 +/- 0.4 vs. 1.0 +/- 0.3 microg mg(-1) wet mass, P < or = 0.05). Glycogen associated with the SR was reduced by 82% in the stimulation protocol (533 +/- 82 vs. 96 +/- 7 microg mg(-1) protein) and by 94% in alpha-amylase treatment (493 +/- 11 vs. 29 +/- 2 microg mg(-1) protein), respectively. Gel electrophoresis and Western blots revealed that the content of Glycogen Debranching Enzyme was reduced by approximately 53% as a result of muscle stimulation and by approximately 46% in alpha-amylase treatment (P < or = 0.05). In addition, Glycogen Debranching Enzyme activity was reduced by 61% in stimulated samples compared with control (20.3 +/- 1.0 vs. 8.0 +/- 1.2 nmol mg(-1) min(-1), respectively), a value consistent with reductions observed from gel electrophoresis and Western blots. CONCLUSION: These results confirm that similar to Glycogen phosphorylase, Glycogen Debranching Enzyme is associated with the skeletal muscle SR and is dissociated under exercise conditions.
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two new mutations in the 3 coding region of the Glycogen Debranching Enzyme in a Glycogen storage disease type iiia ashkenazi jewish patient
Journal of Inherited Metabolic Disease, 1998Co-Authors: R. Parvari, Yuan-tsong Chen, J. Shen, E. Hershkovitz, S. W. MosesAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen Debranching Enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the Glycogen Debranching Enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher Enzyme for its activity and support the suggestion that the putative Glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.
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Isolation and Nucleotide Sequence of Human Liver Glycogen Debranching Enzyme mRNA: Identification of Multiple Tissue-Specific Isoforms
Gene, 1997Co-Authors: Yong Bao, Bing Zhi Yang, Thomas L Dawson, Yuan-tsong ChenAbstract:Abstract Glycogen storage disease type III (GSD-III) is caused by a deficiency of Glycogen Debranching Enzyme (AGL) activity. Patients are found to have deficient AGL activity in both muscle and liver, and also Enzyme deficiency in the liver, but not in muscle. To determine the molecular basis of enzymatic variability in GSD-III and to elucidate the mechanism for control of tissue-specific expression of AGL, we previously cloned and sequenced the human muscle AGL cDNA. Here we report the isolation and nucleotide sequence of liver AGL cDNA and the tissue distribution of the isoform mRNAs. The predominant form of human liver AGL cDNA (isoform 1) contained 400 bp of 5′ untranslated region, 4596 bp of coding region, and 2371 bp of 3′ untranslated region. The liver AGL mRNA sequence was identical to the previously published muscle sequence (isoform 5) for most of the length, except for the 5′ end, in which the liver sequence diverged completely from the muscle sequence. The divergence began with the transcription start point and extended 82 nucleotides downstream from the translation initiation codon. Six isoforms of AGL mRNA were identified and sequenced from liver and muscle. These isoforms differed only at the 5′ end. Tissue distribution studies showed that liver, kidney and lymphoblastoid cells expressed predominantly isoform 1; whereas muscle and heart expressed not only isoform 1, but also muscle-specific isoform mRNAs (isoforms 2, 3 and 4). Defining tissue-specific AGL isoform mRNAs is an important step toward understanding the molecular basis of enzymatic variability in GSD-III.
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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
European Journal of Human Genetics, 1997Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Shimon Moses, Aaron Lerner, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen-Debranching Enzyme (AGL). The overall incidence of the disease is about 1:100,000 life births in the USA; however, it is unusually frequent among North African Jews in Israel (prevalence 1:5,400, carrier prevalence 1:35). All North African Jewish GSD III patients examined have both liver and muscle involvement. While all patients showed the characteristic features related to the liver Enzyme deficiency, the peripheral muscular impairment varied from minimal to severe, with neuromuscular involvement. A single mutation in the AGL gene, the deletion of T at position 4,455 (4),455delT) in homozygous form, was found in this patient population. The mutation 4,455delT results in the change of 17 amino acids at the carboxy terminus of the AGL protein (1),486–1,502) and truncation of the last 30 amino acids of the normal AGL 1,532 amino acids. The mutation appears to be ethnic specific as it was not seen in 18 patients of different ethnic origins. This is the first report of a mutation in the AGL gene affecting a considerable number of GSD III patients in a defined population.
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Polymorphic markers of the Glycogen Debranching Enzyme gene allowing linkage analysis in families with Glycogen storage disease type III.
Journal of medical genetics, 1997Co-Authors: J. Shen, Yong Bao, Hui Ming Liu, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD-III), an autosomal recessive disease, is caused by deficient Glycogen Debranching Enzyme (GDE) activity. We identified three polymorphic markers in the GDE gene using single strand conformation polymorphism (SSCP) analysis and DNA sequencing. They were -10G/A in the 5' non-translated region of exon 3,2001 + 8C/T in intron 16, and 3199C/T (P1067S) in exon 25. Two polymorphic markers (-10G/A and 2001 + 8C/T) were highly informative in both controls and GSD-III patients with heterozygosity values of 0.50 and 0.46, respectively. The third marker (3199C/T) had a heterozygosity value of 0.26. Restriction analysis of the PCR amplified genomic DNA products in two GSD-III families showed for the first time the potential use of these markers for carrier detection and prenatal diagnosis in this disease.
Minoru Okubo - One of the best experts on this subject based on the ideXlab platform.
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Liver cirrhosis treated by living donor liver transplantation in a patient with AGL mutation c.2607-2610delATTC and c.1672dupA
Clinica chimica acta; international journal of clinical chemistry, 2013Co-Authors: Yuichi Kondo, Toshio Murase, Hiromi Usui, Mika Ishige-wada, Misao Owada, Minoru OkuboAbstract:Glycogen storage disease type III (GSD III) is an inherited disorder characterized by the accumulation of abnormal Glycogen in the liver. Hepatic manifestations were considered as improving with age; however, patients live longer and liver cirrhosis is being recognized. We report a patient of GSD IIIa with liver cirrhosis, which was treated successfully by living donor liver transplantation. The patient proved to be a compound heterozygote for a novel small deletion c.2607-2610delATTC and a known duplication c.1672dupA in AGL, a gene coding Glycogen Debranching Enzyme responsible for GSD III. Molecular diagnosis helped clinical decision-making.
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Distinct mutations in the Glycogen Debranching Enzyme found in Glycogen storage disease type III lead to impairment in diverse cellular functions
Human molecular genetics, 2009Co-Authors: Alan Cheng, Minoru Okubo, Kaoru Omichi, Mei Zhang, Alan R. SaltielAbstract:Glycogen storage disease type III (GSDIII) is a metabolic disorder characterized by a deficiency in the Glycogen Debranching Enzyme, amylo-1,6-glucosidase,4-a-glucanotransferase (AGL). Patients with GSDIII commonly exhibit hypoglycemia, along with variable organ dysfunction of the liver, muscle or heart tissues. The AGL protein binds to Glycogen through its C-terminal region, and possesses two separate domains for the transferase and glucosidase activities. Most causative mutations are nonsense, and how they affect the Enzyme is not well understood. Here we investigated four rare missense mutations to determine the molecular basis of how they affect AGL function leading to GSDIII. The L620P mutant primarily abolishes transferase activity while the R1147G variant impairs glucosidase function. Interestingly, mutations in the carbohydrate-binding domain (CBD; G1448R and Y1445ins) are more severe in nature, leading to significant loss of all enzymatic activities and carbohydrate binding ability, as well as enhancing targeting for proteasomal degradation. This region (Y1445‐G1448R) displays virtual identity across human and bacterial species, suggesting an important role that has been conserved throughout evolution. Our results clearly indicate that inactivation of either enzymatic activity is sufficient to cause GSDIII disease and suggest that the CBD of AGL plays a major role to coordinate its functions and regulation by the ubiquitin‐proteasome system.
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Heterogeneous mutations in the Glycogen-Debranching Enzyme gene are responsible for Glycogen storage disease type IIIa in Japan.
Human genetics, 2000Co-Authors: Minoru Okubo, Asako Horinishi, M. Takeuchi, Yoichi Suzuki, Nobuo Sakura, Yukihiro Hasegawa, T. Igarashi, K. Goto, Hideki Tahara, S. UchimotoAbstract:Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disorder caused by deficiency of the Glycogen-Debranching Enzyme (AGL). Recent studies of the AGL gene have revealed the prevalent mutations in North African Jewish and Caucasian populations, but whether these common mutations are present in other ethnic groups remains unclear. We have investigated eight Japanese GSD IIIa patients from seven families and identified seven mutations, including one splicing mutation (IVS14+1G→T) previously reported by us, together with six novel ones: a nonsense mutation (L124X), a splice site mutation (IVS29–1G→C), a 1-bp deletion (587delC), a 2-bp deletion (4216–4217delAG), a 1-bp insertion (2072–2073insA), and a 3-bp insertion (4735–4736insTAT). The last mutation results in insertion of a tyrosine residue at a putative Glycogen-binding site, and the rest are predicted to cause synthesis of truncated proteins lacking the Glycogen-binding site at the carboxyl terminal. Thirteen novel polymorphisms have also been revealed in this study: three amino acid substitutions (R387Q, G1115R, and E1343 K), one silent point mutation (L298L), one nucleotide change in the 5'-noncoding region, and eight nucleotide changes in introns. Haplotype analysis with combinations of these polymorphic markers showed L124X, IVS14+1G→T, and 4216–4217delAG to be on different haplotypes. These results demonstrate the importance of the integrity of the carboxy terminal domain in the AGL protein and the molecular heterogeneity of GSD IIIa in Japan.
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Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the Glycogen Debranching Enzyme gene found in a homozygous patient.
Human mutation, 1999Co-Authors: Minoru Okubo, Asako Horinishi, Fumio Kanda, Keiichi Takahashi, Shiho Okuda, Kazuo Chihara, Toshio MuraseAbstract:Several different mutations in the Glycogen-Debranching Enzyme gene AGL have been found in patients with Glycogen storage disease type III (GSD III) to date, but no missense mutations have been reported for GSD III, only nonsense, splicing, and deletion/insertion lesions. Here we describe a novel G1448R missense mutation in a Japanese GSD IIIa patient from a consanguineous family. Sequence analysis of cDNA from the patient' liver specimen revealed two separate nucleotide changes: a G-to-A transition at nucleotide 3737 in exon 26 (3737G>A) and a G-to-C transversion at nucleotide 4742 in exon 33 (4742G>C), both of which result in substitution of glycine by arginine (G1115R and G1448R). Because homo-zygotes for G1115R were found in healthy controls, G1115R seems to be a polymorphism. Restriction fragment length polymorphism analysis with Bsa JI showed that the patient was homozygous for G1448R and that none of the normal controls had the mutation. This missense mutation is located at a putative Glycogen-binding site that is indispensable for Enzyme activity. Thus, G1448R is likely to be the causative mutation in this patient. This is the first report of a missense mutation associated with GSD III. Hum Mutat 14:542–543, 1999. © 1999 Wiley-Liss, Inc.
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A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12-->G) but no exon 3 mutations in the Glycogen Debranching Enzyme gene in a homozygous patient with Glycogen storage disease type IIIb.
Human genetics, 1998Co-Authors: Minoru Okubo, Yoshiko Aoyama, Asako Horinishi, Norimasa Nakamura, Masaji Hashimoto, Yuzo Endo, Toshio MuraseAbstract:Genetic deficiency of the Glycogen-Debranching Enzyme (debrancher) causes Glycogen storage disease type III (GSD III), which is divided into two subtypes: IIIa and IIIb. In GSD IIIb, Glycogen accumulates only in the liver, whereas both liver and muscles are involved in GSD IIIa. The molecular basis for the differences between the two subtypes has not been fully elucidated. Recently, mutations in exon 3 of the debrancher gene were reported to be specifically associated with GSD IIIb. However, we describe a homozygous GSD IIIb patient without mutations in exon 3. Analysis of the patient’s debrancher cDNA revealed an 11-bp insertion in the normal sequence. An A to G transition at position –12 upstream of the 3′ splice site of intron 32 (IVS 32 A–12→G) was identified in the patient’s debrancher gene. No mutations were found in exon 3. Mutational analysis of the family showed the patient to be homozygous for this novel mutation as well as three polymorphic markers. Furthermore, the mother was heterozygous and the parents were first cousins. The acceptor splice site mutation created a new 3′ splice site and resulted in insertion of an 11-bp intron sequence between exon 32 and exon 33 in the patient’s debrancher mRNA. The predicted mutant Enzyme was truncated by 112 amino acids as a result of premature termination. These findings suggested that a novel IVS 32 A–12→G mutation caused GSD IIIb in this patient.
Toshio Murase - One of the best experts on this subject based on the ideXlab platform.
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Liver cirrhosis treated by living donor liver transplantation in a patient with AGL mutation c.2607-2610delATTC and c.1672dupA
Clinica chimica acta; international journal of clinical chemistry, 2013Co-Authors: Yuichi Kondo, Toshio Murase, Hiromi Usui, Mika Ishige-wada, Misao Owada, Minoru OkuboAbstract:Glycogen storage disease type III (GSD III) is an inherited disorder characterized by the accumulation of abnormal Glycogen in the liver. Hepatic manifestations were considered as improving with age; however, patients live longer and liver cirrhosis is being recognized. We report a patient of GSD IIIa with liver cirrhosis, which was treated successfully by living donor liver transplantation. The patient proved to be a compound heterozygote for a novel small deletion c.2607-2610delATTC and a known duplication c.1672dupA in AGL, a gene coding Glycogen Debranching Enzyme responsible for GSD III. Molecular diagnosis helped clinical decision-making.
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Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the Glycogen Debranching Enzyme gene found in a homozygous patient.
Human mutation, 1999Co-Authors: Minoru Okubo, Asako Horinishi, Fumio Kanda, Keiichi Takahashi, Shiho Okuda, Kazuo Chihara, Toshio MuraseAbstract:Several different mutations in the Glycogen-Debranching Enzyme gene AGL have been found in patients with Glycogen storage disease type III (GSD III) to date, but no missense mutations have been reported for GSD III, only nonsense, splicing, and deletion/insertion lesions. Here we describe a novel G1448R missense mutation in a Japanese GSD IIIa patient from a consanguineous family. Sequence analysis of cDNA from the patient' liver specimen revealed two separate nucleotide changes: a G-to-A transition at nucleotide 3737 in exon 26 (3737G>A) and a G-to-C transversion at nucleotide 4742 in exon 33 (4742G>C), both of which result in substitution of glycine by arginine (G1115R and G1448R). Because homo-zygotes for G1115R were found in healthy controls, G1115R seems to be a polymorphism. Restriction fragment length polymorphism analysis with Bsa JI showed that the patient was homozygous for G1448R and that none of the normal controls had the mutation. This missense mutation is located at a putative Glycogen-binding site that is indispensable for Enzyme activity. Thus, G1448R is likely to be the causative mutation in this patient. This is the first report of a missense mutation associated with GSD III. Hum Mutat 14:542–543, 1999. © 1999 Wiley-Liss, Inc.
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A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12-->G) but no exon 3 mutations in the Glycogen Debranching Enzyme gene in a homozygous patient with Glycogen storage disease type IIIb.
Human genetics, 1998Co-Authors: Minoru Okubo, Yoshiko Aoyama, Asako Horinishi, Norimasa Nakamura, Masaji Hashimoto, Yuzo Endo, Toshio MuraseAbstract:Genetic deficiency of the Glycogen-Debranching Enzyme (debrancher) causes Glycogen storage disease type III (GSD III), which is divided into two subtypes: IIIa and IIIb. In GSD IIIb, Glycogen accumulates only in the liver, whereas both liver and muscles are involved in GSD IIIa. The molecular basis for the differences between the two subtypes has not been fully elucidated. Recently, mutations in exon 3 of the debrancher gene were reported to be specifically associated with GSD IIIb. However, we describe a homozygous GSD IIIb patient without mutations in exon 3. Analysis of the patient’s debrancher cDNA revealed an 11-bp insertion in the normal sequence. An A to G transition at position –12 upstream of the 3′ splice site of intron 32 (IVS 32 A–12→G) was identified in the patient’s debrancher gene. No mutations were found in exon 3. Mutational analysis of the family showed the patient to be homozygous for this novel mutation as well as three polymorphic markers. Furthermore, the mother was heterozygous and the parents were first cousins. The acceptor splice site mutation created a new 3′ splice site and resulted in insertion of an 11-bp intron sequence between exon 32 and exon 33 in the patient’s debrancher mRNA. The predicted mutant Enzyme was truncated by 112 amino acids as a result of premature termination. These findings suggested that a novel IVS 32 A–12→G mutation caused GSD IIIb in this patient.
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a novel point mutation in an acceptor splice site of intron 32 ivs32 a 12 g but no exon 3 mutations in the Glycogen Debranching Enzyme gene in a homozygous patient with Glycogen storage disease type iiib
Human Genetics, 1998Co-Authors: Minoru Okubo, Yoshiko Aoyama, Asako Horinishi, Norimasa Nakamura, Masaji Hashimoto, Yuzo Endo, Toshio MuraseAbstract:Genetic deficiency of the Glycogen-Debranching Enzyme (debrancher) causes Glycogen storage disease type III (GSD III), which is divided into two subtypes: IIIa and IIIb. In GSD IIIb, Glycogen accumulates only in the liver, whereas both liver and muscles are involved in GSD IIIa. The molecular basis for the differences between the two subtypes has not been fully elucidated. Recently, mutations in exon 3 of the debrancher gene were reported to be specifically associated with GSD IIIb. However, we describe a homozygous GSD IIIb patient without mutations in exon 3. Analysis of the patient’s debrancher cDNA revealed an 11-bp insertion in the normal sequence. An A to G transition at position –12 upstream of the 3′ splice site of intron 32 (IVS 32 A–12→G) was identified in the patient’s debrancher gene. No mutations were found in exon 3. Mutational analysis of the family showed the patient to be homozygous for this novel mutation as well as three polymorphic markers. Furthermore, the mother was heterozygous and the parents were first cousins. The acceptor splice site mutation created a new 3′ splice site and resulted in insertion of an 11-bp intron sequence between exon 32 and exon 33 in the patient’s debrancher mRNA. The predicted mutant Enzyme was truncated by 112 amino acids as a result of premature termination. These findings suggested that a novel IVS 32 A–12→G mutation caused GSD IIIb in this patient.
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A Novel Donor Splice Site Mutation in the Glycogen Debranching Enzyme Gene Is Associated with Glycogen Storage Disease Type III
Biochemical and Biophysical Research Communications, 1996Co-Authors: Minoru Okubo, Yoshiko Aoyama, Toshio MuraseAbstract:Abstract Analysis of Glycogen Debranching Enzyme (debrancher) cDNA from a patient with Glycogen storage disease type III revealed a deletion of 124 base pairs. A donor splice site mutation (IVS G +1 to T) was identified in the patient's debrancher gene, which caused exon skipping of the upstream exon and resulted in a truncated Enzyme due to premature termination. Mutational analysis of the patient's family showed that this point mutation was inherited from the father. Southern blot analysis of the patient's genomic DNA showed an additional, unique Eco RI fragment of 5.8 kb, which was inherited from the mother. These results suggested that the patient was a compound heterozygote for the donor splice site mutation, which is the first identified in the debrancher gene, and had a genetic defect relating to an aberrant 5.8-kb Eco RI fragment.
J. Shen - One of the best experts on this subject based on the ideXlab platform.
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Two new mutations in the 3′ coding region of the Glycogen Debranching Enzyme in a Glycogen storage disease type IIIa Ashkenazi Jewish patient
Journal of Inherited Metabolic Disease, 1998Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Y. T. Chen, S. W. MosesAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen Debranching Enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the Glycogen Debranching Enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher Enzyme for its activity and support the suggestion that the putative Glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.
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two new mutations in the 3 coding region of the Glycogen Debranching Enzyme in a Glycogen storage disease type iiia ashkenazi jewish patient
Journal of Inherited Metabolic Disease, 1998Co-Authors: R. Parvari, Yuan-tsong Chen, J. Shen, E. Hershkovitz, S. W. MosesAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen Debranching Enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the Glycogen Debranching Enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher Enzyme for its activity and support the suggestion that the putative Glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.
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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
European Journal of Human Genetics, 1997Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Shimon Moses, Aaron Lerner, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen-Debranching Enzyme (AGL). The overall incidence of the disease is about 1:100,000 life births in the USA; however, it is unusually frequent among North African Jews in Israel (prevalence 1:5,400, carrier prevalence 1:35). All North African Jewish GSD III patients examined have both liver and muscle involvement. While all patients showed the characteristic features related to the liver Enzyme deficiency, the peripheral muscular impairment varied from minimal to severe, with neuromuscular involvement. A single mutation in the AGL gene, the deletion of T at position 4,455 (4),455delT) in homozygous form, was found in this patient population. The mutation 4,455delT results in the change of 17 amino acids at the carboxy terminus of the AGL protein (1),486–1,502) and truncation of the last 30 amino acids of the normal AGL 1,532 amino acids. The mutation appears to be ethnic specific as it was not seen in 18 patients of different ethnic origins. This is the first report of a mutation in the AGL gene affecting a considerable number of GSD III patients in a defined population.
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Polymorphic markers of the Glycogen Debranching Enzyme gene allowing linkage analysis in families with Glycogen storage disease type III.
Journal of medical genetics, 1997Co-Authors: J. Shen, Yong Bao, Hui Ming Liu, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD-III), an autosomal recessive disease, is caused by deficient Glycogen Debranching Enzyme (GDE) activity. We identified three polymorphic markers in the GDE gene using single strand conformation polymorphism (SSCP) analysis and DNA sequencing. They were -10G/A in the 5' non-translated region of exon 3,2001 + 8C/T in intron 16, and 3199C/T (P1067S) in exon 25. Two polymorphic markers (-10G/A and 2001 + 8C/T) were highly informative in both controls and GSD-III patients with heterozygosity values of 0.50 and 0.46, respectively. The third marker (3199C/T) had a heterozygosity value of 0.26. Restriction analysis of the PCR amplified genomic DNA products in two GSD-III families showed for the first time the potential use of these markers for carrier detection and prenatal diagnosis in this disease.
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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
Human mutation, 1997Co-Authors: J. Shen, Yong Bao, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD-III) is an autosomal recessive disease resulting from deficient Glycogen Debranching Enzyme (GDE) activity. A child with GDE deficient in both liver and muscle (GSD-IIIa) had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly and died at 4 years of age. Analysis of the GDE gene in this child by single-strand conformation polymorphism, followed by direct DNA sequencing and restriction analysis, revealed an insertion of a nucleotide A into position 4529 of the GDE cDNA (4529insA). This insertion resulted in substitution of a tyrosine to a stop codon at amino acid 1510 (Y1510X). The 4529insA mutation appeared to be homozygous in this patient and was not found in 20 unrelated controls or 18 other GSD-III patients (14 GSD-IIIa and 4 GSD-IIIb). This is the first identification of a disease mutation in this gene, and the data suggest that homozygous 4529insA may be associated with a severe phenotype in GSD-IIIa.
R. Parvari - One of the best experts on this subject based on the ideXlab platform.
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Two new mutations in the 3′ coding region of the Glycogen Debranching Enzyme in a Glycogen storage disease type IIIa Ashkenazi Jewish patient
Journal of Inherited Metabolic Disease, 1998Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Y. T. Chen, S. W. MosesAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen Debranching Enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the Glycogen Debranching Enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher Enzyme for its activity and support the suggestion that the putative Glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.
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two new mutations in the 3 coding region of the Glycogen Debranching Enzyme in a Glycogen storage disease type iiia ashkenazi jewish patient
Journal of Inherited Metabolic Disease, 1998Co-Authors: R. Parvari, Yuan-tsong Chen, J. Shen, E. Hershkovitz, S. W. MosesAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen Debranching Enzyme (AGL). We report the finding of two new mutations in a GSD IIIa Ashkenazi Jewish patient. Both mutations are insertion of an adenine into a stretch of 8 adenines towards the 3′ end of the coding region: one at position 3904 (3904insA) in exon 30, the second at position 4214 (4214insA) in exon 32. The mutations cause frameshifts and premature terminations of the Glycogen Debranching Enzyme, the first causing a frameshift at amino acid 1304, the second causing a frameshift at amino acid 1408 of the total of 1532. These mutations demonstrate the importance of the 125 amino acids at the carboxy-terminus of the debrancher Enzyme for its activity and support the suggestion that the putative Glycogen binding domain is located in the carboxy-terminus of the AGL. The mutations cause distinctive single-strand conformation polymorphism (SSCP) patterns enabling easy detection.
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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
European Journal of Human Genetics, 1997Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Shimon Moses, Aaron Lerner, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen-Debranching Enzyme (AGL). The overall incidence of the disease is about 1:100,000 life births in the USA; however, it is unusually frequent among North African Jews in Israel (prevalence 1:5,400, carrier prevalence 1:35). All North African Jewish GSD III patients examined have both liver and muscle involvement. While all patients showed the characteristic features related to the liver Enzyme deficiency, the peripheral muscular impairment varied from minimal to severe, with neuromuscular involvement. A single mutation in the AGL gene, the deletion of T at position 4,455 (4),455delT) in homozygous form, was found in this patient population. The mutation 4,455delT results in the change of 17 amino acids at the carboxy terminus of the AGL protein (1),486–1,502) and truncation of the last 30 amino acids of the normal AGL 1,532 amino acids. The mutation appears to be ethnic specific as it was not seen in 18 patients of different ethnic origins. This is the first report of a mutation in the AGL gene affecting a considerable number of GSD III patients in a defined population.
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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
European journal of human genetics : EJHG, 1997Co-Authors: R. Parvari, J. Shen, E. Hershkovitz, Shimon Moses, Aaron Lerner, Yuan-tsong ChenAbstract:Glycogen storage disease type III (GSD III) is an autosomal recessive disease caused by the deficiency of Glycogen-Debranching Enzyme (AGL). The overall incidence of the disease is about 1:100,000 life births in the USA; however, it is unusually frequent among North African Jews in Israel (prevalence 1:5,400, carrier prevalence 1:35). All North African Jewish GSD III patients examined have both liver and muscle involvement. While all patients showed the characteristic features related to the liver Enzyme deficiency, the peripheral muscular impairment varied from minimal to severe, with neuromuscular involvement. A single mutation in the AGL gene, the deletion of T at position 4,455 (4,455delT) in homozygous form, was found in this patient population. The mutation 4,455delT results in the change of 17 amino acids at the carboxy terminus of the AGL protein (1,486-1,502) and truncation of the last 30 amino acids of the normal AGL 1,532 amino acids. The mutation appears to be ethnic specific as it was not seen in 18 patients of different ethnic origins. This is the first report of a mutation in the AGL gene affecting a considerable number of GSD III patients in a defined population.