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Título :	Análisis molecular del gen PAX6 en pacientes mexicanos con aniridia congénita: informe de cuatro nuevas mutaciones. Molecular analysis of the PAX6 gene in Mexican patients with congenital aniridia: report of four novelmutations.
Creador:	Villarroel CE
Nivel de acceso:	Open access
Palabras clave :	Grupo de ascendencia Continental nativo americano - genética Aniridia - genética Proteínas del ojo - genética Proteínas Homeodomain - genética Mutación - genética Mutación Missense American Native Continental Ancestry Group - genetics Aniridia - genetics Eye Proteins - genetics Homeodomain Proteins - genetics Mutation - genetics Mutation, Missense - genetics Genética Mutación genetics mutation
Descripción :	PURPOSE: Paired box gene 6 (PAX6) heterozygous mutations are well known to cause congenital non-syndromic aniridia. These mutations produce primarily protein truncations and have been identified in approximately 40%-80% of all aniridia cases worldwide. In Mexico, there is only one previous report describing three intragenic deletions in five cases. In this study, we further analyze PAX6 variants in a group of Mexican aniridia patients and describe associated ocular findings. METHODS: We evaluated 30 nonrelated probands from two referral hospitals. Mutations were detected by single-strand conformation polymorphism (SSCP) and direct sequencing, and novel missense mutations and intronic changes were analyzed by in silico analysis. One intronic variation (IVS2+9G>A), which in silico analysis suggested had no pathological effects, was searched in 103 unaffected controls. RESULTS: Almost all cases exhibited phenotypes that were at the severe end of the aniridia spectrum with associated ocular alterations such as nystagmus, macular hypoplasia, and congenital cataracts. The mutation detection rate was 30%. Eight different mutations were identified: four (c.184_188dupGAGAC, c.361T>C, c.879dupC, and c.277G>A) were novel, and four (c.969C>T, IVS6+1G>C, c.853delC, and IVS7-2A>G) have been previously reported. The substitution at position 969 was observed in two patients. None of the intragenic deletions previously reported in Mexican patients were found. Most of the mutations detected predict either truncation of the PAX6 protein or conservative amino acid changes in the paired domain. We also detected two intronic non-pathogenic variations, IVS9-12C>T and IVS2+9G>A, that had been previously reported. Because the latter variation was considered potentially pathogenic, it was analyzed in 103 healthy Mexican newborns where we found an allelic frequency of 0.1116 for the A allele. CONCLUSIONS: This study adds four novel mutations to the worldwide PAX6 mutational spectrum, and reaffirms the finding that c.969C>T is one of the three more frequent causal mutations in aniridia cases. It also provides evidence that IVS2+9G>A is an intronic change without pathogenic effect.
Colaborador(es) u otros Autores:	Villanueva-Mendoza C  Orozco L  Alcántara-Ortigoza MA  Jiménez DF  Ordaz JC  González-del Angel A
Fecha de publicación :	2008
Tipo de publicación:	Artículo
Formato:	pdf
Fuente:	Mol Vis.  14():1650-58
URI :	http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2614
Idioma:	eng
Aparece en las colecciones:	Artículos

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