A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem

Boneh, Avihu; Korman, Stanley H.; Sato, Kenichi; Kanno, Junko; Matsubara, Yoichi; Lerer, Israela; Ben‐Neriah, Ziva; Kure, Shigeo

doi:10.1007/s10038-005-0243-y

Cited by 18 publications

(11 citation statements)

References 17 publications

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“…In those countries there are common mutations and many homozygotes for each common mutation. A GLDC missense mutation (p.564I) has been identified in Finland , and a GLDC missense mutation (p.M1 T) and AMT missense mutation (p.H42R) have been found in Israel [Boneh et al, 2005;Flusser et al, 2005].…”

Section: Discussionmentioning

confidence: 98%

“…The GLDC mutations reported to date include the S564I mutation that is prevalent in Finnish patients , the R515S mutation found in 5% of Caucasian patients [Toone et al, 2000], microdeletions , large deletions [Takayanagi et al, 2000;Sellner et al, 2005], one abnormal splicing [Flusser et al, 2005], one nonsense mutation [Sellner et al, 2005], and 10 missense mutations [Toone et al, 2002;Korman et al, 2004;Kure et al, 2004;Boneh et al, 2005;Dinopoulos et al, 2005]. The AMT gene (MIM] 238310) mutations identified to date include nine missense mutations [Nanao et al, 1994[Nanao et al, , 1994aKure et al, 1998;Toone et al, 2000Toone et al, , 2001Toone et al, , 2003], one microdeletion [Kure et al, 1998[Kure et al, , 1998b, and one splicing mutation [Toone et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive mutation analysis ofGLDC,AMT, andGCSHin nonketotic hyperglycinemia

et al. 2006

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Nonketotic hyperglycinemia (NKH) is an inborn error of metabolism characterized by accumulation of glycine in body fluids and various neurological symptoms. NKH is caused by deficiency of the glycine cleavage multi-enzyme system with three specific components encoded by GLDC, AMT, and GCSH. We undertook the first comprehensive screening for GLDC, AMT, and GCSH mutations in 69 families (56, six, and seven families with neonatal, infantile, and late-onset type NKH, respectively). GLDC or AMT mutations were identified in 75% of neonatal and 83% of infantile families, but not in late-onset type NKH. No GCSH mutation was identified in this study. GLDC mutations were identified in 36 families, and AMT mutations were detected in 11 families. In 16 of the 36 families with GLDC mutations, mutations were identified in only one allele despite sequencing of the entire coding regions. The GLDC gene consists of 25 exons. Seven of the 32 GLDC missense mutations were clustered in exon 19, which encodes the cofactor-binding site Lys754. A large deletion involving exon 1 of the GLDC gene was found in Caucasian, Oriental, and black families. Multiple origins of the exon 1 deletion were suggested by haplotype analysis with four GLDC polymorphisms. This study provides a comprehensive picture of the genetic background of NKH as it is known to date.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Comprehensive mutation analysis ofGLDC,AMT, andGCSHin nonketotic hyperglycinemia

et al. 2006

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“…Of note, the effect of initiator methionine codon alteration on protein production appears to depend on the specific gene and ranges from normal protein expression, to N‐terminal deletions (resulting from use of a downstream methionine), to reduced or no detectable protein. The effect on mRNA levels is also variable [Boneh et al, 2005]. After the initiator methionine, the next in frame ATG codon in GAA is located at amino acid position 122.…”

Section: Discussionmentioning

confidence: 99%

Predicting cross‐reactive immunological material (CRIM) status in Pompe disease using GAA mutations: Lessons learned from 10 years of clinical laboratory testing experience

Bali¹,

Goldstein²,

Banugaria³

et al. 2012

American J of Med Genetics Pt C

116

128

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Enzyme replacement therapy (ERT) for Pompe disease using recombinant acid alpha-glucosidase (rhGAA) has resulted in increased survival although the clinical response is variable. Cross Reactive Immunological Material (CRIM)-negative status has been recognized as a poor prognostic factor. CRIM-negative patients make no GAA protein and develop sustained high antibody titers to ERT that render the treatment ineffective. Antibody titers are generally low for the majority of CRIM-positive patients and there is typically a better clinical outcome. Because immunomodulation has been found to be most effective in CRIM-negative patients prior to, or shortly after, initiation of ERT, knowledge of CRIM status is important before ERT is begun. We have analyzed 243 patients with infantile Pompe disease using a Western blot method for determining CRIM status and using cultured skin fibroblasts. Sixty-one out of 243 (25.1%) patients tested from various ethnic backgrounds were found to be CRIM-negative. We then correlated the CRIM results with GAA gene mutations where available (52 CRIM-negative and 88 CRIM-positive patients). We found that, in most cases, CRIM status can be predicted from GAA mutations, potentially circumventing the need for invasive skin biopsy and time wasted in culturing cells in the future. Continued studies in this area will help to increase the power of GAA gene mutations in predicting CRIM status as well as possibly identifying CRIM-positive patients who are at risk for developing high antibody titers.

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“…Of note, the effect of initiator methionine codon alteration on protein production appears to depend on the specific gene and ranges from normal protein expression, to N-terminal deletions (resulting from use of a downstream methionine), to reduced or no detectable protein. The effect on mRNA levels is also variable [Boneh et al, 2005]. After the initiator methionine, the next in frame ATG codon in GAA is located at amino acid position 122.…”

Section: Missense Mutationsmentioning

confidence: 99%

Predicting Cross Reactive Immunological Material (CRIM) Status in Pompe Disease Using GAA Mutations: Lessons Learned from 10 Years of Clinical Laboratory Testing Experience

Bali

Goldstein

Banugaria

et al. 2012

Molecular Genetics and Metabolism

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Enzyme replacement therapy (ERT) for Pompe disease using recombinant acid alpha-glucosidase (rhGAA) has resulted in increased survival although the clinical response is variable. Cross-reactive immunological material (CRIM)-negative status has been recognized as a poor prognostic factor. CRIM-negative patients make no GAA protein and develop sustained high antibody titers to ERT that render the treatment ineffective. Antibody titers are generally low for the majority of CRIM-positive patients and there is typically a better clinical outcome. Because immunomodulation has been found to be most effective in CRIM-negative patients prior to, or shortly after, initiation of ERT, knowledge of CRIM status is important before ERT is begun. We have analyzed 243 patients with infantile Pompe disease using a Western blot method for determining CRIM status and using cultured skin fibroblasts. Sixty-one out of 243 (25.1%) patients tested from various ethnic backgrounds were found to be CRIM-negative. We then correlated the CRIM results with GAA gene mutations where available (52 CRIMnegative and 88 CRIM-positive patients). We found that, in most cases, CRIM status can be predicted from GAA mutations, potentially circumventing the need for invasive skin biopsy and time wasted in culturing cells in the future. Continued studies in this area will help to increase the power of GAA gene mutations in predicting CRIM status as well as possibly identifying CRIM-positive patients who are at risk for developing high antibody titers.

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A single nucleotide substitution that abolishes the initiator methionine codon of the GLDC gene is prevalent among patients with glycine encephalopathy in Jerusalem

Cited by 18 publications

References 17 publications

Comprehensive mutation analysis ofGLDC,AMT, andGCSHin nonketotic hyperglycinemia

Comprehensive mutation analysis ofGLDC,AMT, andGCSHin nonketotic hyperglycinemia

Predicting cross‐reactive immunological material (CRIM) status in Pompe disease using GAA mutations: Lessons learned from 10 years of clinical laboratory testing experience

Predicting Cross Reactive Immunological Material (CRIM) Status in Pompe Disease Using GAA Mutations: Lessons Learned from 10 Years of Clinical Laboratory Testing Experience

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