PAX6 allelic heterogeneity in Mexican congenital aniridia patients: expanding the mutational spectrum with seven novel pathogenic variants.
Clin Exp Ophthalmol
; 45(9): 875-883, 2017 12.
Article
en En
| MEDLINE
| ID: mdl-28488383
IMPORTANCE: The importance of the study was to describe the clinical characteristics and mutational analysis of Mexican patients with aniridia. BACKGROUND: Aniridia is a panocular hereditary eye disease caused by mutations in the PAX6 transcription factor. Mutation detection rate is highly variable ranging from 30% to 90% in different populations. Very few studies have been published about the PAX6 mutational analysis in aniridia patients from Mexico. In order to establish a more representative PAX6 mutational frequency in the country, a cohort of 22 Mexican unrelated aniridia probands were analysed in this study. DESIGN: Case series. PARTICIPANTS: A total of 22 Mexican probands with bilateral isolated aniridia and their available relatives were included. METHODS: Sanger sequencing was used for the mutational analysis of all coding exons and flanking intronic regions of PAX6. MAIN OUTCOME MEASURES: Clinical characteristics and results of PAX6 mutational analysis in probands with aniridia and available family members. RESULTS: Molecular analysis of PAX6 in 22 index cases with aniridia allowed the identification of a total of 16 different mutations. Seven of these pathogenic variants are novel, including c.183C>G, p.(Y61*); c.718delC, p.(R240Efs*3); c.1149_1152delTCAG, p.(P385Wfs*139); c.257_266delAAATAGCCCA, p.(K86Sfs*35); c.836_843dupGCAACACA p.(P282Afs*86); c.1032+2_1032+3insT; and c.141+2T>A. Inter and intrafamilial phenotypic heterogeneity was found. CONCLUSIONS AND RELEVANCE: The mutational diagnostic rate in this series was 77%, which is comparable with reports from other populations. Importantly, no founder mutations were identified in this case series. Our results add 7 novel PAX6 pathogenic variants to the aniridia-related mutational spectrum and reveal considerable PAX6 allelic heterogeneity in this population.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
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Aniridia
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Factor de Transcripción PAX6
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Mutación
Tipo de estudio:
Incidence_studies
/
Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Mexico
Idioma:
En
Revista:
Clin Exp Ophthalmol
Asunto de la revista:
OFTALMOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
México
Pais de publicación:
Australia