Summary
Molybdenum cofactor deficiency (MOCOD) is a rare inherited metabolic disorder resulting in the combined deficiency of aldehyde oxidase (AO, EC 1.2.3.1), xanthine dehydrogenase (XDH, EC 1.1.1.204), and sulfite oxidase (SUOX, EC 1.8.3.1). The majority of patients typically present soon after birth with intractable seizures, developmental delay and lens dislocation and do not survive early childhood. Milder cases have been reported. We report an unusual mutation in the MOCS1 gene associated with a relatively mild clinical phenotype, in a patient who presented with normal uric acid (UA) levels in plasma. We also report a new MOCS1 mRNA splice variant in the 5′ region of the gene. MOCS1 genomic DNA and cDNA from peripheral blood leukocytes were sequenced. MOCS1 mRNA splice variants were amplified with fluorescently labelled primers and quantitated. A novel homozygous mutation MOCS1c.1165+6T > C in intron 9 resulting in miss-splicing of exon 9 was found. Multiple alternatively spliced MOCS1 transcripts have been previously reported. A new MOCS1 transcript in the 5′ – exon 1 region was identified in both patient and controls. This new transcript derived from the Larin variant and lacked exon 1 d.
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Abbreviations
- AO:
-
aldehyde oxidase
- cPMP:
-
cyclic pyranopterin monophosphate
- ESE/ISE:
-
exonic/intronic splicing enhancers
- ESS/ISS:
-
exonic/intronic splicing silencers
- GEPH:
-
gephyrin
- GTP:
-
guanosine triphosphate
- hnRNP:
-
heterogeneous nuclear ribonucleoproteins
- HX:
-
hypoxanthine
- ISOD:
-
isolated sulfite oxidase deficiency
- MoCo:
-
molybdenum cofactor
- MOCOD:
-
molybdenum cofactor deficiency
- MPT:
-
molybdopterin
- ORF:
-
open reading frame
- snRNP:
-
small nuclear ribonucleoproteins
- SRp:
-
serine rich proteins
- ss:
-
splice site
- SUOX:
-
sulfite oxidase
- UA:
-
uric acid
- X:
-
xanthine
- XDH:
-
xanthine dehydrogenase
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Acknowledgements
We acknowledge funding from the Purine Research Fund, Guy’s and St Thomas’ Charity.
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Communicating editor: John Christodoulou
Competing interests: None declared
References to electronic databases: http://ast.bioinfo.tau.ac.il/SpliceSiteFrame.htm. http://www.ebi.ac.uk/asd-srv. http://rulai.cshl.edu/cgi-bin/tolls/ESE3/esefinder.cgi. http://www.ncbi.nlm.nih.gov/ (for Homo sapiens MOCS1 [AJ224328]). Aldehyde oxidase: EC 1.2.3.1. Sulfite oxidase: EC 1.8.3.1. Xanthine dehydrogenase: EC 1.1.1.204.
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Arenas, M., Fairbanks, L.D., Vijayakumar, K. et al. An unusual genetic variant in the MOCS1 gene leads to complete missplicing of an alternatively spliced exon in a patient with molybdenum cofactor deficiency. J Inherit Metab Dis 32, 560–569 (2009). https://doi.org/10.1007/s10545-009-1151-7
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DOI: https://doi.org/10.1007/s10545-009-1151-7