Characterization of seven novel mutations in seven patients with GAMT deficiency.

C. B. Item, S. Mercimek-Mahmutoglu, R. Battini, C. Edlinger-Horvat, C. Stromberger, O. Bodamer, A. Mühl, M. A. Vilaseca, H. Korall, S. Stöckler-Ipsiroglu

Research output: Contribution to journalArticle

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Abstract

Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. So far, six mutations have been identified in seven patients. We investigated seven new patients by screening the promoter, 3'UTR, and six exons and exon/intron boundaries using direct sequencing and denaturing gradient gel electrophoresis. The clinical and biochemical phenotype was characterized by scoring the degree of main clinical manifestations and by determination of urinary guanidinoacetate concentrations and of GAMT activity in fibroblasts / lymphoblasts, respectively. We identified 7 novel mutations, including c.64dupG (exon 1; 4/14 alleles); c.59G>C (exon 1; 3/14 alleles); c.491delG (exon 5; 2/14 alleles); c.160G>C (exon 1; 2/14 alleles); and c.152A>C (exon 1; 1/14 alleles); c.526dupG (exon 5; 1/14 alleles); c.521G>A (exon 5; 1/14 alleles), and two polymorphisms c.626C>T (exon 6) and c.459+71G>A (intron 4). Frameshift and missense mutations in exon 1 were prevalent in the 4 patients with the severe phenotype, however a clear genotype-phenotype correlation has not been established in the limited number of patients characterized so far.

Original languageEnglish
JournalHuman Mutation
Volume23
Issue number5
StatePublished - May 1 2004

Fingerprint

Exons
Mutation
Alleles
Creatine
Introns
Guanidinoacetate N-Methyltransferase
Guanidinoacetate methyltransferase deficiency
Phenotype
Denaturing Gradient Gel Electrophoresis
Frameshift Mutation
Genetic Association Studies
3' Untranslated Regions
Missense Mutation
Intellectual Disability
Epilepsy
Fibroblasts

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Item, C. B., Mercimek-Mahmutoglu, S., Battini, R., Edlinger-Horvat, C., Stromberger, C., Bodamer, O., ... Stöckler-Ipsiroglu, S. (2004). Characterization of seven novel mutations in seven patients with GAMT deficiency. Human Mutation, 23(5).

Characterization of seven novel mutations in seven patients with GAMT deficiency. / Item, C. B.; Mercimek-Mahmutoglu, S.; Battini, R.; Edlinger-Horvat, C.; Stromberger, C.; Bodamer, O.; Mühl, A.; Vilaseca, M. A.; Korall, H.; Stöckler-Ipsiroglu, S.

In: Human Mutation, Vol. 23, No. 5, 01.05.2004.

Research output: Contribution to journalArticle

Item, CB, Mercimek-Mahmutoglu, S, Battini, R, Edlinger-Horvat, C, Stromberger, C, Bodamer, O, Mühl, A, Vilaseca, MA, Korall, H & Stöckler-Ipsiroglu, S 2004, 'Characterization of seven novel mutations in seven patients with GAMT deficiency.', Human Mutation, vol. 23, no. 5.
Item CB, Mercimek-Mahmutoglu S, Battini R, Edlinger-Horvat C, Stromberger C, Bodamer O et al. Characterization of seven novel mutations in seven patients with GAMT deficiency. Human Mutation. 2004 May 1;23(5).
Item, C. B. ; Mercimek-Mahmutoglu, S. ; Battini, R. ; Edlinger-Horvat, C. ; Stromberger, C. ; Bodamer, O. ; Mühl, A. ; Vilaseca, M. A. ; Korall, H. ; Stöckler-Ipsiroglu, S. / Characterization of seven novel mutations in seven patients with GAMT deficiency. In: Human Mutation. 2004 ; Vol. 23, No. 5.
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