Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patients.
We report twelve novel mutations in patients with isolated sulfite oxidase deficiency. The mutations are in SUOX, the gene that encodes the molybdohemoprotein sulfite oxidase. These include two frameshift mutations, a four-basepair deletion (562del4) and a single-basepair insertion (113insC), both resulting in premature termination. Nonsense mutations predicting Y343X and Q364X substitutions were identified in a homozygous state in three patients, the latter in two sibs. The remaining eight are missense mutations generating single amino acid substitutions. From the position of the substituted residues, seven of these mutations are considered to be causative of the enzyme deficiency: I201L, R211Q, G305S, R309H, K322R, Q339R, and W393R. The eighth, a C>T transition, predicts an R319C substitution, which could affect the binding of the molybdenum cofactor and thus severely reduce sulfite oxidase activity. This mutation, however, is downstream of a frameshift mutation and is therefore not the causative mutation in this individual.
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. jean_johnson@biochem.duke.edu
Jean L
JL
Johnson
Katharine E
KE
Coyne
Robert M
RM
Garrett
Marie-Therese
MT
Zabot
Claude
C
Dorche
Caroline
C
Kisker
K V
KV
Rajagopalan
D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008664:Metal Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency / Q000235:genetics*
D004247:DNA; D050862:Oxidoreductases Acting on Sulfur Group Donors