Identification of Four Novel PCDH19 Mutations and Prediction of Their Functional Impact

Annals of Human Genetics

Volumn 78, Issue 6, 2014, Pages 389-398

  Leonardi, Emanuela ^a   Sartori, Stefano ^a   Vecchi, Marilena ^a   Bettella, Elisa ^a   Polli, Roberta ^a   De Palma, Luca ^a   Boniver, Clementina ^a   Murgia, Alessandra ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

EFMR; Epilepsy; in silico analysis; Pathogenicity; PCDH19

Indexed keywords

CADHERIN; PCDH19 PROTEIN, HUMAN;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CHEMICAL STRUCTURE; CHILD; EPILEPSY; FEMALE; GENETICS; HUMAN; INFANT; MISSENSE MUTATION; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; ONSET AGE; PHENOTYPE; PRESCHOOL CHILD; PROTEIN TERTIARY STRUCTURE; YOUNG ADULT;

AGE OF ONSET; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; CADHERINS; CHILD; CHILD, PRESCHOOL; DNA MUTATIONAL ANALYSIS; EPILEPSY; FEMALE; HUMANS; INFANT; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PHENOTYPE; PROTEIN STRUCTURE, TERTIARY; YOUNG ADULT;

EID: 84908207041     PISSN: 00034800     EISSN: 14691809     Source Type: Journal    
DOI: 10.1111/ahg.12082     Document Type: Article

References (44)

1. Adzhubei, I., Jordan, D. M. & Sunyaev, S. R. (2013) Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet Chapter 7, Unit7.20.
2. Ashkenazy, H., Erez, E., Martz, E., Pupko, T. & Ben-Tal, N. (2010) ConSurf 2010: Calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res 38(Web Server issue), W529-533.
3. Bairoch, A., Apweiler, R., Wu, C. H., Barker, W. C., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M. J., Natale, D. A., O'Donovan, C., Redaschi, N. & Yeh, L.-S. L. (2005) The Universal Protein Resource (UniProt). Nucleic Acids Res 33(Database issue), D154-159.
4. Bettella, E., Di Rosa, G., Polli, R., Leonardi, E., Tortorella, G., Sartori, S. & Murgia, A. (2013) Early-onset epileptic encephalopathy in a girl carrying a truncating mutation of the ARX gene: Rethinking the ARX phenotype in females. Clin Genet 84, 82-85.
5. Boggon, T. J., Murray, J., Chappuis-Flament, S., Wong, E., Gumbiner, B. M. & Shapiro, L. (2002) C-cadherin ectodomain structure and implications for cell adhesion mechanisms. Science 296, 1308-1313.
6. Bromberg, Y., Yachdav, G. & Rost, B. (2008) SNAP predicts effect of mutations on protein function. Bioinformatics 24, 2397-2398.
7. Canutescu, A. A., Shelenkov, A. A. & Dunbrack, R. L., Jr (2003) A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci 12, 2001-2014.
8. Capriotti, E., Calabrese, R. & Casadio, R. (2006) Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information. Bioinformatics 22, 2729-2734.
9. Chappuis-Flament, S., Wong, E., Hicks, L. D., Kay, C. M. & Gumbiner, B. M. (2001) Multiple cadherin extracellular repeats mediate homophilic binding and adhesion. J Cell Biol 154, 231-243.
10. Depienne, C., Bouteiller, D., Keren, B., Cheuret, E., Poirier, K., Trouillard, O., Benyahia, B., Quelin, C., Carpentier, W., Julia, S., Afenjar, A., Gautier, A., Rivier, F., Meyer, S., Berquin, P., Helias, M., Py, I., Rivera, S., Bahi-Buisson, N., Gourfinkel-An, I., Cazeneuve, C., Ruberg, M., Brice, A., Nabbout, R. & LeGuern, E. (2009) Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet 5, e1000381.
11. Depienne, C. & LeGuern, E. (2012) PCDH19-related infantile epileptic encephalopathy: An unusual X-linked inheritance disorder. Human Mutat 33, 627-634.
12. Depienne, C., Trouillard, O., Bouteiller, D., Gourfinkel-An, I., Poirier, K., Rivier, F., Berquin, P., Nabbout, R., Chaigne, D., Steschenko, D., Gautier, A., Hoffman-Zacharska, D., Lannuzel, A., Lackmy-Port-Lis, M., Maurey, H., Dusser, A., Bru, M., Gilbert-Dussardier, B., Roubertie, A., Kaminska, A., Whalen, S., Mignot, C., Baulac, S., Lesca, G., Arzimanoglou, A. & LeGuern, E. (2011) Mutations and deletions in PCDH19 account for various familial or isolated epilepsies in females. Hum Mutat 32, E1959-E1975.
13. Dibbens, L. M., Kneen, R., Bayly, M. A., Heron, S. E., Arsov, T., Damiano, J. A., Desai, T., Gibbs, J., McKenzie, F., Mulley, J. C., Ronan, A. & Scheffer, I. E. (2011) Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations. Neurology 76, 1514-1519.
14. Dibbens, L. M., Tarpey, P. S., Hynes, K., Bayly, M. A., Scheffer, I. E., Smith, R., Bomar, J., Sutton, E., Vandeleur, L., Shoubridge, C., Edkins, S., Turner, S. J., Stevens, C., O'Meara, S., Tofts, C., Barthorpe, S., Buck, G., Cole, J., Halliday, K., Jones, D., Lee, R., Madison, M., Mironenko, T., Varian, J., West, S., Widaa, S., Wray, P., Teague, J., Dicks, E., Butler, A., Menzies, A., Jenkinson, A., Shepherd, R., Gusella, J. F., Afawi, Z., Mazarib, A., Neufeld, M. Y., Kivity, S., Lev, D., Lerman-Sagie, T., Korczyn, A. D., Derry, C. P., Sutherland, G. R., Friend, K., Shaw, M., Corbett, M., Kim, H.-G., Geschwind, D. H., Thomas, P., Haan, E., Ryan, S., McKee, S., Berkovic, S. F., Futreal, P. A., Stratton, M. R., Mulley, J. C. & Gécz, J. (2008) X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet 40, 776-781.
15. Emond, M. R., Biswas, S., Blevins, C. J. & Jontes, J. D. (2011) A complex of Protocadherin-19 and N-cadherin mediates a novel mechanism of cell adhesion. J Cell Biol 195, 1115-1121.
16. Fokkema, I. F. A. C., Taschner, P. E. M., Schaafsma, G. C. P., Celli, J., Laros, J. F. J. & den Dunnen, J. T. (2011) LOVD v.2.0: The next generation in gene variant databases. Hum Mutat 32, 557-563.
17. Hynes, K., Tarpey, P., Dibbens, L. M., Bayly, M. A., Berkovic, S. F., Smith, R., Raisi, Z. A., Turner, S. J., Brown, N. J., Desai, T. D., Haan, E., Turner, G., Christodoulou, J., Leonard, H., Gill, D., Stratton, M. R., Gecz, J. & Scheffer, I. E. (2010) Epilepsy and mental retardation limited to females with PCDH19 mutations can present de novo or in single generation families. J Med Genet 47, 211-216.
18. Jamal, S. M., Basran, R. K., Newton, S., Wang, Z. & Milunsky, J. M. (2010) Novel de novo PCDH19 mutations in three unrelated females with epilepsy female restricted mental retardation syndrome. Am J Med Genet Part A 152A, 2475-2481.
19. Juberg, R. C. & Hellman, C. D. (1971) A new familial form of convulsive disorder and mental retardation limited to females. J Pediatr 79, 726-732.
20. Katoh, K., Asimenos, G. & Toh, H. (2009) Multiple alignment of DNA sequences with MAFFT. Methods Mol Biol 537, 39-64.
21. Kim, S.-Y., Chung, H. S., Sun, W. & Kim, H. (2007) Spatiotemporal expression pattern of non-clustered protocadherin family members in the developing rat brain. Neuroscience 147, 996-1021.
22. Leonardi, E., Andreazza, S., Vanin, S., Busolin, G., Nobile, C. & Tosatto, S. C. E. (2011) A computational model of the LGI1 protein suggests a common binding site for ADAM proteins. PloS One 6, e18142.
23. Marini, C., Mei, D., Parmeggiani, L., Norci, V., Calado, E., Ferrari, A., Moreira, A., Pisano, T., Specchio, N., Vigevano, F., Battaglia, D. & Guerrini, R. (2010) Protocadherin 19 mutations in girls with infantile-onset epilepsy. Neurology 75, 646-653.
24. Minor, D. L., Jr & Kim, P. S. (1994) Measurement of the beta-sheet-forming propensities of amino acids. Nature 367, 660-663.
25. Morishita, H., Umitsu, M., Murata, Y., Shibata, N., Udaka, K., Higuchi, Y., Akutsu, H., Yamaguchi, T., Yagi, T. & Ikegami, T. (2006) Structure of the cadherin-related neuronal receptor/protocadherin-alpha first extracellular cadherin domain reveals diversity across cadherin families. J Biol Chem 281, 33650-33663.
26. Morishita, H. & Yagi, T. (2007) Protocadherin family: Diversity, structure, and function. Curr Opin Cell Biol 19, 584-592.
27. Nagar, B., Overduin, M., Ikura, M. & Rini, J. M. (1996) Structural basis of calcium-induced E-cadherin rigidification and dimerization. Nature 380, 360-364.
28. Ng, P. C. & Henikoff, S. (2003) SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31, 3812-3814.
29. Patel, S. D., Ciatto, C., Chen, C. P., Bahna, F., Rajebhosale, M., Arkus, N., Schieren, I., Jessell, T. M., Honig, B., Price, S. R. & Shapiro, L. (2006) Type II cadherin ectodomain structures: Implications for classical cadherin specificity. Cell 124, 1255-1268.
30. Pertz, O., Bozic, D., Koch, A. W., Fauser, C., Brancaccio, A. & Engel, J. (1999) A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation. EMBO J 18, 1738-1747.
31. Prakasam, A., Chien, Y.-H., Maruthamuthu, V. & Leckband, D. E. (2006) Calcium site mutations in cadherin: Impact on adhesion and evidence of cooperativity. Biochemistry 45, 6930-6939.
32. Redies, C., Vanhalst, K. & Roy, F. van (2005) delta-Protocadherins: Unique structures and functions. Cell Mol Life Sci 62, 2840-2852.
33. Richards, C. S., Bale, S., Bellissimo, D. B., Das, S., Grody, W. W., Hegde, M. R., Lyon, E., Ward, B. E. & Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee (2008) ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007. Genet Med 10, 294-300.
34. Ryan, S. G., Chance, P. F., Zou, C. H., Spinner, N. B., Golden, J. A. & Smietana, S. (1997) Epilepsy and mental retardation limited to females: An X-linked dominant disorder with male sparing. Nat Genet 17, 92-95.
35. Specchio, N., Marini, C., Terracciano, A., Mei, D., Trivisano, M., Sicca, F., Fusco, L., Cusmai, R., Darra, F., Bernardina, B. D., Bertini, E., Guerrini, R. & Vigevano, F. (2011) Spectrum of phenotypes in female patients with epilepsy due to protocadherin 19 mutations. Epilepsia 52, 1251-1257.
36. Stenson, P. D., Mort, M., Ball, E. V., Howells, K., Phillips, A. D., Thomas, N. S. & Cooper, D. N. (2009) The human gene mutation database: 2008 update. Genome Med 1, 13.
37. Tai, K., Kubota, M., Shiono, K., Tokutsu, H. & Suzuki, S. T. (2010) Adhesion properties and retinofugal expression of chicken protocadherin-19. Brain Res 1344, 13-24.
38. Thusberg, J. & Vihinen, M. (2009) Pathogenic or not? And if so, then how? Studying the effects of missense mutations using bioinformatics methods. HumMutat 30, 703-714.
39. Tosatto, S. C. E., Bindewald, E., Hesser, J. & Männer, R. (2002) A divide and conquer approach to fast loop modeling. Protein Eng 15, 279-286.
40. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E. & Berendsen, H. J. C. (2005) GROMACS: Fast, flexible, and free. J Comput Chem 26, 1701-1718.
41. Van Harssel, J. J. T., Weckhuysen, S., van Kempen, M. J. A., Hardies, K., Verbeek, N. E., de Kovel, C. G. F., Gunning, W. B., van Daalen, E., de Jonge, M. V., Jansen, A. C., Vermeulen, R. J., Arts, W. F. M., Verhelst, H., Fogarasi, A., de Rijk-van Andel, J. F., Kelemen, A., Lindhout, D., De Jonghe, P., Koeleman, B. P. C., Suls, A. & Brilstra, E. H. (2013) Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders. Neurogenetics 14, 23-34.
42. Vendome, J., Posy, S., Jin, X., Bahna, F., Ahlsen, G., Shapiro, L. & Honig, B. (2011) Molecular design principles underlying β-strand swapping in the adhesive dimerization of cadherins. Nat Struct Mol Biol 18, 693-700.
43. Walsh, I., Minervini, G., Corazza, A., Esposito, G., Tosatto, S. C. E. & Fogolari, F. (2012) Bluues server: Electrostatic properties of wild-type and mutated protein structures. Bioinformatics 28, 2189-2190.
44. Wolverton, T. & Lalande, M. (2001) Identification and characterization of three members of a novel subclass of protocadherins. Genomics 76, 66-72.