PAH mutational spectrum: still expanding
Laura Vilarinho, Sofia Esteves, Elisabete Ramos, António Amorim, Luisa Azevedo
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DOI: 10.4236/ojgen.2011.12002   PDF    HTML     7,066 Downloads   13,411 Views   Citations

Abstract

Phenylketonuria (PKU, MIM 261600) is the most common inborn error of amino acid metabolism. To date, a total of more than 500 mutations have been associated with the disease. In this report, the novel p.Glu182Lys mutation, found in a Portuguese family in combination with the previously reported p.Leu 348Val, is presented and its putative deleterious impact discussed.

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Vilarinho, L. , Esteves, S. , Ramos, E. , Amorim, A. and Azevedo, L. (2011) PAH mutational spectrum: still expanding. Open Journal of Genetics, 1, 9-12. doi: 10.4236/ojgen.2011.12002.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Loeber, J.G. (2007) Neonatal screening in Europe; the situation in 2004. Journal of Inherited Metabolic Disease, 30, 430-438. doi:10.1007/s10545-007-0644-5
[2] Williams, R.A., Mamotte, C.D. and Burnett, J.R. (2008) Penhylketonuria: An inborn error of phenylalanine me-tabolism. Clinical Biochemistry, 29, 31-41.
[3] Woo, S.L., Lidsky, A.S., Gütler, F., Chandra, T. and Rob-son, K.J. (1983) Cloned human phenylalanine hy-droxylase gene allows prenatal diagnosis and carrier detection of classical phenylketonuria. Nature, 306, 151-155. doi:10.1038/306151a0
[4] Scriver, C.R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Waters, P.J., Ryan, S., McDonald, D. and Sarkissian, C. (2003) PAHdb 2003: What a locus-specific knowledgebase can do. Hu-man Mutation, 21, 333-334. http://www.pahdb.mcgill. Ca
[5] Human Genetic Mutation Database. http://www.hgmd.cf.ac.uk/
[6] Lee, D.H., Koo, S.K., Lee, K.S., Yeon, Y.J., Oh, H.J., Kim, S.W., Lee, S.J., Kim, S.S., Lee, J.E., Jo, I. and Jung, S.C. (2004) The molecular basis of phenylketonuria in Koreans. Journal of Human Genetics, 49, 617-621. doi:10.1007/s10038-004-0197-5
[7] Daniele, A., Cardillo, G., Pennino, C., Carbone, M.T., Scognamiglio, D., Correra, A., Pignero, A., Castaldo, G. and Salvatore, F. (2007) Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: A 96% detection rate with ten novel mutations. Annals of Human Genetics, 71, 185-193. doi:10.1111/j.1469-1809.2006.00328.x
[8] Zschocke, J. (2003) Phenylketonuria mutations in Europe. Human Mutation, 21, 345-356. doi:10.1002/humu.10192
[9] Kasnauskiene, J., Giannattasio, S., Lattanzio, P., Cimba-listiene, L. and Kucinskas, V. (2003) The molecular basis of phenylketonuria in Lithuania. Human Mutation, 21, 398-403. doi:10.1002/humu.9113
[10] Zschocke, J. and Hoffmann, G.F. (1999) Phenylketonuria mutations in Germany. Human Mutation, 104, 390-398. doi:10.1007/s004390050973
[11] Guldberg, P., Levy, H.L., Hanley, W.B., Koch, R., Mata-lon, R., Rouse, B.M., Trefz, F., De la Cruz, F., Henriksen, K.F. and Guttler, F. (1996) Phenylalanine hydroxylase gene mutations in the United States: Report from the Maternal PKU Collaborative Study. The American Jour-nal of Human Genetics, 59, 684-694.
[12] Eiken, H.G., Knappskog, P.M., Boman, H., Thune, K.S., Kaada, G., Motzfeldt, K. and Apold, J. (1996) Relative frequency, heterogeneity and geographic clustering of PKU mutations in Norway. European Journal of Human Genetics, 4, 205-213.
[13] Rivera, I., Leandro, P., Lichter-Konecki, U., Almeida, I.T. and Lechner, M.C. (1998) Population genetics of hyper-phenylalaninaemia resulting from phenylalanine hydrox-ylase deficiency in Portugal. Journal of Medical Genetics, 35, 301-304. doi:10.1136/jmg.35.4.301
[14] Vilarinho, L., Queirós, A., Leandro, P., Almeida, I.T. and Rivera I. (2006) Fenilcetonúria Revisitada. Arquivos de Medicina, 20, 161-171.
[15] Santos, L.L., Castro-Magalh?es, M., Fonseca, C.G., Starling, A.L.P., Januário, J.N., Aguiar, M.J.B. and Car-valho, M.R.S. (2008) PKU in minas Gerais state, Brazil: Mutation analysis. Annals of Human Genetics, 72, 774-779. doi:10.1111/j.1469-1809.2008.00476.x
[16] Ensembl Genome Browser. http://www.ensembl.org
[17] Edgar, R.C. (2004) MUSCLE: Multiple sequence align-ment with high accuracy and high throughput. Nucleic Acids Research, 32, 1792-1797. doi:10.1093/nar/gkh340
[18] Drummond, A.J., Ashton, B., Buxton, S., Cheung, M., Cooper, A., Heled, J., Kearse, M., Moir, R., Stones-Ha- vas, S., Sturrock, S., Thierer, T. and Wilson A. (2010) Inspirational Software for Biologiests, Geneious. http://www.geneious.com
[19] Eisensmith, R.C. and Woo, S.L. (1995) Molecular genet-ics of phenylketonuria: From molecular anthropology to gene therapy. Advances in Genetics, 32, 199-271. doi:10.1016/S0065-2660(08)60206-0
[20] Polyphen: Prediction of functional effect of human nsSNPs. http://genetics.bwh.harvard.edu/pph
[21] Sorting Intolerant from Tolerant (SIFT). http://blocks.fhcrc.org/sift/SIFT.html
[22] Dipple, K.M. and McCabe, E.R.B. (2000) Phenotypes of patients with “simple” mendelian disorders are complex traits: Thresholds, modifiers, and systems dynamics. The American Journal of Human Genetics, 66, 1729-1735. doi:10.1086/302938
[23] Scriver C.R. and Waters, P.J. (1999) Monogenic traits are not simple: Lessons from phenylketonuria. Trends in Genetics, 15, 267-272. doi:10.1016/S0168-9525(99)01761-8
[24] Cooper, D.N., Chen, J., Ball, E.V., Howells, K., Mort, M., Philips, A.D., Chuzhanova, N., Krawczak, M., Kehrer- Sawatzki, H. and Stenson, P.D. (2010) Genes, mutations, and human inherited disease at the dawn of the age of personalized genomics. Human Mutation, 31, 631-655. doi:10.1002/humu.21260

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