Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molybdenum cofactor (MoCo) deficiency leads to a combined deficiency of the molybdoenzymes sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase. Effective therapy is not available for this rare disease, which results in neonatal seizures and other neurological symptoms identical to those of sulphite oxidase deficiency. It is an autosomal recessive trait and leads to early childhood death. Biosynthesis of MoCo can be divided into the formation of a precursor and its subsequent conversion to the organic moiety of MoCo by molybdopterin synthase. These two steps are the molecular basis of the two observed complementation groups A and B and of two types of MoCo deficiency with an identical phenotype. MOCS1 is defective in the majority of patients (group A) and was shown to encode two enzymes functioning in the formation of a precursor. The corresponding transcript is bicistronic with two consecutive open reading frames (ORFs). MOCS2 encodes the small and large subunits of molybdopterin synthase via a single transcript with two overlapping reading frames. This gene carries lesions in the B complementation group less frequently observed in patients. Both genes, MOCS1 and MOCS2, share the unusual bicistronic architecture, have identical and very low expression profiles and extremely conserved C-terminal ends in their 5'-ORF. These observations point to a novel form of microcompartmentalization and render the MOCS genes ideal candidates for a somatic gene therapy approach.
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PMID:Genetics of molybdenum cofactor deficiency. 1074 56

Molybdenum cofactor deficiency is a rare inborn error of metabolism with generally severe symptoms, most often including neonatal seizures and severe developmental delay. We describe a patient with an unusually mild form of the disease. Two mutations in MOCS2A (molybdenum cofactor synthesis enzyme 2A) were identified: a single base change, 16C > T, that predicts a Q6X substitution on one allele and a 19G > T transversion that predicts a valine to phenylalanine substitution, V7F, on the second. It is postulated that the milder clinical symptoms result from a low level of residual molybdopterin synthase activity derived from the 19G > T allele.
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PMID:Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency. 1174 50

(1) Background: Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. (2) Methods: Our paper aimed to delineate the disease genotype by presenting another patient, in whom a novel, in-frame variant within the MOCS2 gene was identified. (3) Results: Exome sequencing led to the identification of a novel variant in the MOCS2 gene-c.472_477del of unknown significance (VUS). (4) Conclusions: To prove the clinical significance of the mentioned variant, analysis of the possible mutation consequences on molecular level with the use of the available crystal structure of the human molybdopterin synthase complex was of great importance. Moreover, a potential pathomechanism resulting from a molecular defect was presented, giving original insight into the current knowledge on this rare disease, including treatment options.
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PMID:Proteins Structure Models in the Evaluation of Novel Variant (C.472_477del) in the MOCS2 Gene. 3306 91