A novel familial mutation in the PCSK1 gene that alters the oxyanion hole residue of proprotein convertase 1/3 and impairs its enzymatic activity

PLoS ONE

Volumn 9, Issue 10, 2014, Pages

  Wilschanski, Michael ^a   Abbasi, Montaser ^a   Blanco, Elias ^b,c   Lindberg, Iris ^b   Yourshaw, Michael ^c   Zangen, David ^a   Berger, Itai ^a   Shteyer, Eyal ^a   Pappo, Orit ^a   Bar Oz, Benjamin ^a   Martín, Martin G ^c   Elpeleg, Orly ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; ASPARAGINE; LYSINE; MUTANT PROTEIN; PROPROTEIN CONVERTASE 1; PCSK1 PROTEIN, HUMAN;

ARTICLE; CASE REPORT; CHILD; DIARRHEA; ENDOCRINE DISEASE; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME MECHANISM; ENZYME MODIFICATION; ENZYME RELEASE; EXOME; FEMALE; GENE; GENE MAPPING; GENETIC CODE; HEK293 CELL LINE; HOMOZYGOSITY; HUMAN; HUMAN CELL; HUMAN TISSUE; INFANT; MALE; MUTATIONAL ANALYSIS; NEWBORN; NUCLEOTIDE SEQUENCE; PCSK1 GENE; PRESCHOOL CHILD; SEQUENCE ANALYSIS; SIBLING; GENETICS; METABOLISM; MUTATION; PEDIGREE;

CHILD; DIARRHEA; ENDOCRINE SYSTEM DISEASES; EXOME; FEMALE; HUMANS; INFANT; INFANT, NEWBORN; MALE; MUTATION; PEDIGREE; PROPROTEIN CONVERTASE 1;

EID: 84907486842     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0108878     Document Type: Article

References (36)

1. Canani RB, Terrin G. (2011) Recent progress in congenital diarrheal disorders. Curr Gastroenterol Rep 13: 257-264.
2. Turk E, Zabel B, Mundlos S., Dyer J, Wright E.M. (1991) Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 350: 354-356.
3. Ouwendijk J, Moolenaar CE, Peters W.J., Hollenberg CP, Ginsel LA, et al. (1996) Congenital sucrase-isomaltase deficiency. Identification of a glutamine to proline substitution that leads to a transport block of sucrase-isomaltase in a pre-Golgi compartment. J Clin Invest 97: 633-641.
4. Muller T, Hess MW, Schiefermeier N, Pfaller K., Ebner HL, et al. (2008) MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity. Nat Genet 40: 1163-1165.
5. Sivagnanam M, Mueller JL, Lee H, Chen Z., Nelson SF, et al. (2008) Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology 135: 429-437.
6. Bennett CL, Ochs H.D. (2001) IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenomena. Curr Opin Pediatr 13: 533-538.
7. Wang J, Cortina G, Wu S.V., Tran R., Cho JH, et al. (2006) Mutant neurogenin-3 in congenital malabsorptive diarrhea. N Engl J Med 355: 270-280.
8. Terrin G, Tomaiuolo R, Passariello A., Elce A, Amato F, et al (2012) Congenital diarrheal disorders: an updated diagnostic approach. Int J Mol Sci 13: 4168-4185.
9. Yourshaw M, Solorzano-Vargas RS, Pickett L.A., Lindberg I., Wang J, et al. (2013) Exome Sequencing Finds a Novel PCSK1 Mutation in a Child With Generalized Malabsorptive Diarrhea and Diabetes Insipidus. J Pediatr Gastro-enterol Nutr 57: 759-767.
10. Benzinou M, Creemers JW, Choquet H, Lobbens S., Dina C, et al. (2008) Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet 40: 943-945.
11. Martin MG, Lindberg I, Solorzano-Vargas RS, Wang J., Avitzur Y, et al. (2013) Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. Gastroenterology 145: 138-148.
12. Pickett LA, Yourshaw M, Albornoz V., Chen Z, Solorzano-Vargas RS, et al. (2013) Functional consequences of a novel variant of PCSK1. PLoS One 8: e55065.
13. Farooqi IS, Volders K, Stanhope R., Heuschkel R, White A, et al (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 92: 3369-3373.
14. Jackson RS, Creemers JW, Farooqi I.S., Raffin-Sanson ML, Varro A, et al (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112: 1550-1560.
15. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L., et al. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16: 303-306.
16. Edvardson S, Shaag A, Kolesnikova O., Gomori JM, Tarassov I, et al. (2007) Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 81: 857-862.
17. Blanco EH, Peinado JR, Martín MG, Lindberg I. (2014) Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph. Endocrinology en20132151. [Epub ahead of print]
18. Kumar P, Henikoff S, Ng P.C. (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4: 1073-1081.
19. Adzhubei IA, Schmidt S, Peshkin L., Ramensky VE, Gerasimova A, et al. (2010) A method and server for predicting damaging missense mutations. Nat Methods 7: 248-249.
20. Chun S, Fay J.C. (2009) Identification of deleterious mutations within three human genomes. Genome Res 19: 1553-1561.
21. Reva B, Antipin Y, Sander C. (2011) Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res 39: e118.
22. Schwarz JM, Rodelsperger C, Schuelke M., Seelow D. (2010) Mutation Taster evaluates disease-causing potential of sequence alterations. Nat Methods 7: 575-576.
23. Gonzalez-Perez A., Lopez-Bigas N (2011) Improving the assessment of the outcome of nonsynonymous SNVs with a consensus deleteriousness score, Condel. Am J Hum Genet 88: 440-449.
24. Lopes MC, Joyce C, Ritchie G.R., John SL, Cunningham F, et al. (2012) A combined functional annotation score for non-synonymous variants. Hum Hered 73: 47-51.
25. Genomes Project Consortium, Abecasis GR, Auton A, Brooks LD, DePristo MA, et al. (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491: 56-65.
26. NHLBI Exome Sequencing Project. Exome Variant Server. Volume September 2011. Seattle WA: NHLBI Exome Sequencing Project (ESP), 2011.
27. Berger I, Dor T, Halvardson J., Edvardson S, Shaag A, et al (2012) Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene. Epilepsia 53: 1436-1440.
28. Zupanc ML (2009) Clinical evaluation and diagnosis of severe epilepsy syndromes of early childhood. J Child Neurol 24(8 Suppl): 6S-14S.
29. Mastrangelo M, Leuzzi V. (2012) Genes of early-onset epileptic encephalopa-thies: from genotype to phenotype. Pediatr Neurol 46: 24-31.
30. Bryan P, Pantoliano MW, Quill S.G., Hsiao HY, Poulos T. (1986) Site-directed mutagenesis and the role of the oxyanion hole in subtilisin. Proc Natl Acad Sci U S A 83: 3743-3745.
31. Brenner C, Bevan A, Fuller R.S. (1993) One-step site-directed mutagenesis of the Kex2 protease oxyanion hole. Curr Biol 3: 498-506.
32. Zhou A, Paquet L, Mains R.E. (1995) Structural elements that direct specific processing of different mammalian subtilisin-like prohormone convertases. J Biol Chem 270: 21509-21516.
33. Goodman LJ, Gorman C.M. (1994) Autoproteolytic activation of the mouse prohormone convertase mPC1. Biochem Biophys Res Commun 201: 795-804.
34. Taylor NA, Shennan KI, Cutler D.F., Docherty K. (1997) Mutations within the propeptide, the primary cleavage site or the catalytic site, or deletion of C-terminal sequences, prevents secretion of proPC2 from transfected COS-7 cells. Biochem J 321: 367-373.
35. Scougall K, Taylor NA, Jermany J.L., Docherty K., Shennan K.I. (1998) Differences in the autocatalytic cleavage of pro-PC2 and pro-PC3 can be attributed to sequences within the propeptide and Asp310 of pro-PC2. Biochem J 334: 531-537.
36. Online Mendelian Inheritance in Man OMIMH. Online Mendelian Inheritance in Man, OMIMH. Baltimore, MD: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University.