title: The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations.
abstract: Four new mutations in the cystathionine beta-synthase (CBS) gene have been identified in Italian patients with homocystinuria. The first mutation is a G-to-A transition at base 374 in exon 3, causing an arginine-to-glutamic acid substitution at position 125 of the protein (R125Q). This mutation has been found in homozygosity in a patient partially responsive to pyridoxine treatment. The second mutation is a C-to-T transition at base 770 in exon 7, causing a threonine-to-methionine substitution at amino acid 257 of the protein (T257M). This mutation has been observed in homozygosity in a patient nonresponsive to the cofactor treatment. The third mutation, found in heterozygosity in a patient responsive to pyridoxine treatment, is an insertion of 68 bp in exon 8 at base 844, which introduces a premature termination codon. The fourth mutation is C-to-T transition in exon 2 at base 262, causing a proline-to-serine substitution at position 88 of the protein (P88S). This mutation is carried on a single allele in three affected sisters responsive to the cofactor treatment. In addition, six previously reported mutations (A114V, E131D, P145L, I278T, G307S, and A1224-2C) have been tested in 14 independent Italian families. Mutations A114V and I278T are carried by three and by seven independent alleles, respectively. The other four mutations--including G307S and A1224-2C, common among northern European patients--have not been detected.
authors.affiliation: Department of Pediatrics, Federico II University, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sebastio
authors.forename: M P
authors.initials: MP
authors.lastname: Sperandeo
authors.forename: M
authors.initials: M
authors.lastname: Panico
authors.forename: R
authors.initials: R
authors.lastname: de Franchis
authors.forename: J P
authors.initials: JP
authors.lastname: Kraus
authors.forename: G
authors.initials: G
authors.lastname: Andria
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006712:Homocystinuria / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D003541:Cystathionine beta-Synthase