Copy-Number Variations in EYS: A Significant Event in the Appearance of arRP
Por:
Pieras, JI, Barragan, I, Borrego, S, Audo, I, Gonzalez-Del Pozo, M, Bernal, S, Baiget, M, Zeitz, C, Bhattacharya, SS, Antinolo, G
Publicada:
1 jul 2011
Resumen:
PURPOSE. Autosomal recessive retinitis pigmentosa (arRP) has recently been associated with mutations in a novel gene, EYS, which is a major gene for this disease. All published mutations so far are based on conventional PCR and are not adequate to identify midsized DNA rearrangements. This study was conducted to establish the prevalence of copy-number variations (CNVs) in the EYS gene in a cohort of arRP patients, including individuals in whom only one pathogenic change was detected by PCR-based sequencing.
METHODS. A multiple ligation-dependent probe amplification (MLPA) was used for the molecular genetic analyses of CNVs by a novel EYS-specific kit. PCR-based direct sequencing was used in families where a pathogenic deletion or duplication was identified in one allele. Bioinformatics analyses was undertaken to study the effect of the mutations on protein structure and function.
RESULTS. Six novel pathogenic CNVs were identified. Also, the presence of four midsized deletions was confirmed in patients previously identified. Midsized genomic rearrangements in EYS are disease causing in similar to 4% of the families with no reported mutations and constitute the second pathogenic variation in similar to 15% of cases where a mutation has been detected by direct sequencing.
CONCLUSIONS. This is the first report of a systematic CNV screening of EYS gene in a cohort of arRP patients. Results suggest that midsized genomic rearrangements in EYS gene would be a common event in the appearance of RP phenotype. An efficient and cost-effective strategy validating a novel MLPA kit as a complementary diagnostic method for EYS pathogenic evaluation has been demonstrated. (Invest Ophthalmol Vis Sci. 2011;52:5625-5631) DOI:10.1167/iovs.11-7292
Filiaciones:
Pieras, JI:
Univ Seville, Hosp Univ Virgen del Rocio, Unidad Gest Clin Genet Reprod & Med Fetal, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
CIBERER, Valencia, Spain
Barragan, I:
Univ Seville, Hosp Univ Virgen del Rocio, Unidad Gest Clin Genet Reprod & Med Fetal, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
CIBERER, Valencia, Spain
Borrego, S:
Univ Seville, Hosp Univ Virgen del Rocio, Unidad Gest Clin Genet Reprod & Med Fetal, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
CIBERER, Valencia, Spain
Audo, I:
INSERM, U968, Paris, France
CNRS, UMR 7210, Paris, France
UPMC Univ Paris 06, Inst Vis, UMR S 968, Paris, France
Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM DHOS, Paris, France
Gonzalez-Del Pozo, M:
Univ Seville, Hosp Univ Virgen del Rocio, Unidad Gest Clin Genet Reprod & Med Fetal, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
CIBERER, Valencia, Spain
Bernal, S:
CIBERER, Valencia, Spain
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Baiget, M:
CIBERER, Valencia, Spain
Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona, Spain
Zeitz, C:
INSERM, U968, Paris, France
CNRS, UMR 7210, Paris, France
UPMC Univ Paris 06, Inst Vis, UMR S 968, Paris, France
Bhattacharya, SS:
Andalusian Mol Biol & Regenerat Med Ctr CABIMER, Dept Cellular Therapy & Regenerat Med, Seville 931092, Spain
Antinolo, G:
Univ Seville, Hosp Univ Virgen del Rocio, Unidad Gest Clin Genet Reprod & Med Fetal, CSIC,Inst Biomed Sevilla IBIS, Seville 41013, Spain
CIBERER, Valencia, Spain
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