title: Two new severe mutations causing guanidinoacetate methyltransferase deficiency.
abstract: Primary disorders of creatine metabolism have been only recently described. We report new molecular and biochemical findings obtained from a child affected by guanidinoacetate methyltransferase deficiency. This patient presented with neurological regression, epilepsy, and a movement disorder during the first year of life. HPLC analysis showed high concentrations of guanidinoacetic acid in urine, plasma, and CSF. Molecular analyses of cDNA and genomic DNA revealed two novel mutations, a G insertion following nucleotide 491 of the cDNA (c.491insG) in exon 5 and a transversion at nt -3 in intron 5 (IVS5-3C>G). The c.491insG mutation causes a frameshift and a premature stop codon at the end of the exon. The IVS5-3C>G mutation prevents the splicing of the last exon of the gene precluding the complete maturation of the transcript and, most likely, causes rapid degradation of the mRNA.
authors.affiliation: Department of Experimental Medicine and Pathology, Università "La Sapienza,", Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Carducci
authors.forename: V
authors.initials: V
authors.lastname: Leuzzi
authors.forename: C
authors.initials: C
authors.lastname: Carducci
authors.forename: S
authors.initials: S
authors.lastname: Prudente
authors.forename: L
authors.initials: L
authors.lastname: Mercuri
authors.forename: I
authors.initials: I
authors.lastname: Antonozzi
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004252:DNA Mutational Analysis; D018740:Genetic Heterogeneity; D005998:Glycine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D050937:Guanidinoacetate N-Methyltransferase; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology* / Q000235:genetics*; D008780:Methyltransferases / Q000172:deficiency* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D003404:Creatinine; D008780:Methyltransferases; D050937:Guanidinoacetate N-Methyltransferase; C004946:glycocyamine; D003401:Creatine; D005998:Glycine