Total truncation of the molybdopterin/dimerization domains of SUOX protein in an Arab family with isolated sulfite oxidase deficiency

Abstract

We ascertained a patient with the full-blown phenotype of isolated sulfite oxidase deficiency in a consanguineous Arab family. The proband's phenotype included the presence of intractable seizures in the neonatal period, some dysmorphic features, neuroradiologic findings reminiscent of hypoxic ischemic encephalopathy and rapidly progressive brain destruction leading to severe neurodevelopmental impairment. Biochemically, the patient excreted a large amount of S-sulfocysteine with normal amounts of xanthene and hypoxanthine and had normal plasma uric acid, which was consistent with isolated sulfite oxidase deficiency. We report the identification of the first Arab mutation in SUOX, the gene for sulfite oxidase enzyme, in the ascertained family. The newly identified Arab mutation in the SUOX gene (a single nucleotide deletion, del G1244) is predicted to cause a frame shift at amino acid 117 of the translated protein with the generation of a stop codon and total truncation of the molybdo-pterin- and the dimerizing-domain(s) of SUOX protein expressed from the mutant allele. The identification of this new Arab SUOX mutation should facilitate pre-implantation genetic diagnosis and selection of unaffected embryos for future pregnancy in the ascertained family with the mutation and related families with the same mutation.

Structural Studies of the Molybdenum Center of the Pathogenic R160Q Mutant of Human Sulfite Oxidase by Pulsed EPR Spectroscopy and 17O and 33S Labeling

“…All of the lines observed in these spectra within the frequency window shown were missing in the case of 32 S-R160Q SO, which allows one to assign them to the interaction of Mo(V) with 33 S. The feature of interest in these spectra is the peak at 18 MHz that belongs to one of the interdoublet transitions (| ± 1/2〉 ↔ | ± 3/2〉) of 33 S within the electron spin manifold where the Zeeman and hyperfine interactions approximately cancel each other. The frequency of this transition is: (1) and we can easily estimate the quadrupole coupling constant e 2 Qq/h ≈ 36 MHz, very similar to e 2 Qq/h ≈ 40 MHz found for 33 S-At-SO. 6 Panels a, c, and e in Figure 4 show K a -band hyperfine sublevel correlation (HYSCORE) spectra obtained for Species 1 of 33 S-R160Q SO at the EPR turning points.…”

“…Inherited mutations in SO can result in severe neurological problems, stunted brain growth, and early death. 1 Investigation of the biochemistry of specific mutations has been greatly aided by the development of procedures for producing recombinant human sulfite oxidase (hSO). One of the most extensively studied clinical mutations that causes isolated sulfite oxidase deficiency is Arg 160 to Gln (R160Q), [2][3][4] which results from a single base change (guanine to adenine) in the gene for SO.…”

Molybdenum cofactor and isolated sulphite oxidase deficiencies: Clinical and molecular spectrum among Egyptian patients

“…3 They have been identified in the genes MOCS1 (type A deficiency), MOCS2 (type B deficiency), and in GPHN . 12,14,20 It was documented that the most commonly mutated gene in MoCD patients was the MOCS1 gene, followed by MOCS2 . 19 Reiss et al, 2011 found 99% mutation detection with analysis of the MOCS1 and MOCS2 genes in MoCD diagnosed biochemically.…”

“…The gene for sulfite oxidase maps to chromosome 12q13.2 and mutations in SUOX gene leads to isolated sulfite oxidase deficiency. 14 In the current study, we describe the clinical, biochemical and genetic findings of nine patients with disorders of sulfur-containing amino acid metabolism, upon genetic study, six had MoCD and three had SOD.…”

S-Sulfo-Cysteine is an Endogenous Amino Acid in Neonatal Rat Brain but an Unlikely Mediator of Cysteine Neurotoxicity

“…Cysteine-carbamate is a potent NMDA-receptor agonist and likely to contribute to cysteine toxicity [4]. Another less investigated cysteine-derived compound is the thio-ester S-sulfo-cysteine (SSC), discovered in the urine and blood of a patient with cysteine oxidase deficiency [16][17][18][19][20]. SSC is produced by reaction of inorganic sulfite and cystine by a yet unknown pathway and is a very potent NMDA-receptor agonist [21].…”