Ana Vega

Autonomous University of Barcelona, Cerdanyola del Vallès, Catalonia, Spain

Are you Ana Vega?

Claim your profile

Publications (87)353.7 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence supporting the role of genetic variants in the development of radiation-induced toxicity. However, previous candidate gene association studies failed to elucidate the common genetic variation underlying this phenotype, which could emerge years after the completion of treatment. We performed a genome-wide association study on a Spanish cohort of 741 individuals with prostate cancer treated with external beam radiotherapy (EBRT). The replication cohorts consisted of 633 cases from the UK and 368 cases from North America. One locus comprising TANC1 (lowest unadjusted P value for overall late toxicity = 6.85 × 10(-9), odds ratio (OR) = 6.61, 95% confidence interval (CI) = 2.23-19.63) was replicated in the second stage (lowest unadjusted P value for overall late toxicity = 2.08 × 10(-4), OR = 6.17, 95% CI = 2.25-16.95; Pcombined = 4.16 × 10(-10)). The inclusion of the third cohort gave unadjusted Pcombined = 4.64 × 10(-11). These results, together with the role of TANC1 in regenerating damaged muscle, suggest that the TANC1 locus influences the development of late radiation-induced damage.
    Nature genetics. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondrial common variants (mtSNPs) and the haplogroups defined by them have been inconsistently correlated with increased prostate cancer risk. Here we aimed to investigate the influence of the mitochondrial genetic background on prostate cancer. A total of 15 single-nucleotide polymorphisms (SNPs) representing the common European branches of the mtDNA phylogeny were analyzed in a cohort of 620 Spanish prostate cancer patients and 616 matched population-based controls. Association tests were computed on mtSNPs and haplogroups. None of the evaluated mtSNPs or haplogroups were statistically associated with prostate cancer risk in our Spanish cohort. We show that previous association findings do not rest on solid grounds given that all of them (i) were based on underpowered studies, (ii) did not control for population stratification, (iii) lacked replication/confirmation cohorts, and (iv) and did not control for multiple test corrections. Taken together, a critical reassessment of the previous literature and the results obtained in the present study suggest that mtDNA common European variants are not correlated with increases in the risk for prostate cancer.Journal of Human Genetics advance online publication, 5 June 2014; doi:10.1038/jhg.2014.46.
    Journal of human genetics. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2years after radiotherapy. A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. Quantile-quantile plots show more associations at the P<5×10(-7) level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable.
    Radiotherapy and Oncology 04/2014; · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mitochondrial DNA common variants have been reported to be associated with the development of radiation-induced toxicity. Using a large cohort of patients, we aimed to validate these findings by investigating the potential role of common European mitochondrial DNA SNPs (mtSNPs) to the development of radio-toxicity. Overall acute and late toxicity data were assessed in a cohort of 606 prostate cancer patients by means of Standardized Total Average Toxicity (STAT) score. We carried out association tests between radiation toxicity and a selection of 15 mtSNPs (and the haplogroups defined by them). Statistically significant association between mtSNPs and haplogroups with toxicity could not be validated in our Spanish cohort. The present study suggests that the mtDNA common variants analyzed are not associated with clinically relevant increases in risk of overall radiation-induced toxicity in prostate cancer patients.
    Radiotherapy and Oncology 04/2014; · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose Mitochondrial DNA common variants have been reported to be associated with the development of radiation-induced toxicity. Using a large cohort of patients, we aimed to validate these findings by investigating the potential role of common European mitochondrial DNA SNPs (mtSNPs) to the development of radio-toxicity. Material and methods Overall acute and late toxicity data were assessed in a cohort of 606 prostate cancer patients by means of Standardized Total Average Toxicity (STAT) score. We carried out association tests between radiation toxicity and a selection of 15 mtSNPs (and the haplogroups defined by them). Results Statistically significant association between mtSNPs and haplogroups with toxicity could not be validated in our Spanish cohort. Conclusions The present study suggests that the mtDNA common variants analyzed are not associated with clinically relevant increases in risk of overall radiation-induced toxicity in prostate cancer patients.
    Radiotherapy and Oncology. 01/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the Iberian Peninsula, which includes mainly Spain and Portugal, large genomic rearrangements (LGRs) of BRCA1 and BRCA2 have respectively been found in up to 2.33% and 8.4% of families with hereditary breast and/or ovarian cancer (HBOC) that lack point mutations and small indels. In Galicia (Northwest Spain), the spectrum and frequency of BRCA1/BRCA2 point mutations differs from the rest of the Iberian populations. However, to date there are no Galician frequency reports of BRCA1/BRCA2 LGRs. Here we used multiplex ligation-dependent probe amplification (MLPA) to screen 651 Galician index cases (out of the 830 individuals referred for genetic analysis) without point mutations or small indels. We identified three different BRCA1 LGRs in four families. Two of them have been previously classified as pathogenic LGRs: the complete deletion of BRCA1 (identified in two unrelated families) and the deletion of exons 1 to 13. We also identified the duplication of exons 1 and 2 that is a LGR with unknown pathogenicity. Determination of the breakpoints of the BRCA1 LGRs using CNV/SNP arrays and sequencing identified them as NG_005905.2:g.70536_180359del, NG_005905.2:g.90012_97270dup, and NC_000017.10:g.41230935_41399840delinsAluSx1, respectively; previous observations of BRCA1 exon1-24del, exon1-2dup, and exon1-13del LGRs have not characterized them in such detail. All the BRCA1 LGRs arose from unequal homologous recombination events involving Alu elements. We also detected, by sequencing, one BRCA2 LGR, the Portuguese founder mutation c.156_157insAluYa5. The low frequency of BRCA1 LGRs within BRCA1 mutation carriers in Galicia (2.34%, 95% CI: 0.61-7.22) seems to differ from the Spanish population (9.93%, 95% CI: 6.76-14.27, P-value = 0.013) and from the rest of the Iberian population (9.76%, 95% CI: 6.69-13.94, P-value = 0.014).
    PLoS ONE 01/2014; 9(3):e93306. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Loss-of-function germline mutations in BRCA1 (MIM #113705) confer markedly increased risk of breast and ovarian cancer. The full-length transcript codifies for a protein involved in DNA repair pathways and cell-cycle checkpoints. Several BRCA1 splicing isoforms have been described in public domain databases, but the physiological role (if any) of BRCA1 alternative splicing remains to be established. An accurate description of 'naturally occurring' alternative splicing at this locus is a prerequisite to understand its biological significance. However, a systematic analysis of alternative splicing at the BRCA1 locus is yet to be conducted. Here, the Evidence-Based Network for the Interpretation of Germ-Line Mutant Alleles consortium combines RT-PCR, exon scanning, cloning, sequencing and relative semi-quantification to describe naturally occurring BRCA1 alternative splicing with unprecedented resolution. The study has been conducted in blood-related RNA sources, commonly used for clinical splicing assays, as well as in one healthy breast tissue. We have characterized a total of 63 BRCA1 alternative splicing events, including 35 novel findings. A minimum of 10 splicing events (Δ1Aq, Δ5, Δ5q, Δ8p, Δ9, Δ(9,10), Δ9_11, Δ11q, Δ13p and Δ14p) represent a substantial fraction of the full-length expression level (ranging from 5 to 100%). Remarkably, our data indicate that BRCA1 alternative splicing is similar in blood and breast, a finding supporting the clinical relevance of blood-based in vitro splicing assays. Overall, our data suggest an alternative splicing model in which most non-mutually exclusive alternative splicing events are randomly combined into individual mRNA molecules to produce hundreds of different BRCA1 isoforms
    Human Molecular Genetics 01/2014; · 7.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The term inherited ichthyosis subsumes numerous clinically and aetiologically heterogeneous cornification disorders with Mendelian inheritance patterns. Prior to January 2012, six genes had been identified as having loss-of-function mutations causing autosomal recessive congenital ichthyosis (ARCI): ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4 and TGM1.(1) In a study of ALOX12B, ALOXE3, CYP4F22, NIPAL4 and TGM1 performed in seventeen ARCI families in Galicia (NW Spain),(2,3) about 80% of these families had mutant TGM1 or ALOXE3, while no mutations of NIPAL4, CYP4F22 or ALOX12B were found. We later identified the novel ALOX12B mutation c.1609G>A (p.Val537Met referred to NP_001130.1) in a family with previously undiagnosed ARCI whose affected members were homozygous for this mutation. This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 12/2013; · 3.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: on behalf of the ENIGMA consortium BACKGROUND: Accurate evaluation of unclassified se-quence variants in cancer predisposition genes is essen-tial for clinical management and depends on a multi-factorial analysis of clinical, genetic, pathologic, and bioinformatic variables and assays of transcript length and abundance. The integrity of assay data in turn re-lies on appropriate assay design, interpretation, and reporting. METHODS: We conducted a multicenter investigation to compare mRNA splicing assay protocols used by mem-bers of the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) consor-tium. We compared similarities and differences in re-sults derived from analysis of a panel of breast cancer 1,
    Clinical Chemistry 11/2013; · 7.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: RAD51D mutations have been recently identified in breast (BC) and ovarian (OC) cancer families. Although an aetiological role in OC seems to be present, the association of RAD51D mutations and BC risk is more unclear. We aimed to determine the prevalence of germline RAD51D mutations in Spanish breast/ovarian cancer families negative for BRCA1/BRCA2 mutations. We analyzed 842 index patients: 491 from BC/OC families, 171 BC families, 51 OC families, and 129 patients without family history but with early-onset BC or OC or metachronous BC and OC. Mutation detection was performed with HRM, DHPLC or Sanger sequencing. Three mutations were found in four families with BC and OC cases (0.82%). Two were novel: c.1A>T (p.Met1?) and c.667+2_667+23del, leading to the exon 7 skipping and one previously described: c.674C>T (p.Arg232*). All were present in BC/OC families with only one OC. The c.667+2_667+23del co-segregated in the family with one early onset BC and two bilateral BC cases. We also identified the c.629C>T (p.Ala210Val) variant, which was predicted in silico to be potentially pathogenic. About 1% of the BC and OC Spanish families negative for BRCA1/BRCA2 are carriers of RAD51D mutations. The presence of several BC mutation carriers, albeit in the context of familial OC, suggests an increased risk for BC, which should be taken into account in the follow-up and early detection measures. RAD51D testing should be considered in clinical setting for families with BC and OC, irrespective of the number of OC cases in the family © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2013; · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: X-linked dominant protoporphyria (XLDPP) is a genetic disorder that affects the synthesis of the heme group due to an increase in delta-aminolaevulinate synthase 2 (ALAS2) enzyme activity. Moreover, annular elastolytic giant-cell granuloma (AEGCG) is a rare reactive granulomatous dermatosis, usually associated with actinic damage. An 86-year-old man presented with edematous-erythematous lesions in photoexposed areas of the face and on the dorsum of both hands. Protoporphyrin levels in serum and feces were significantly elevated and a heterozygous frameshift mutation in the exon 11 of the ALAS2 gene: c.1706-1709del (p.Glu569GlyfsX24) was identified. Concomitantly, we observed an annular plaque with raised borders on the back of his right hand, clinically and histologically compatible with a diagnosis of AEGCG. Skin lesions disappeared only upon use of a physical sunscreen. We report two rare photodermatoses in an elderly patient and discuss the significance of dermal elastic fiber damage induced by the XLDPP as a main triggering factor of AEGCG. © 2013 S. Karger AG, Basel.
    Dermatology 10/2013; · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene cause Fanconi anemia (FA) subtype FA-Q. To investigate the possible role of ERCC4 in breast and ovarian cancer susceptibility, as occurs with other FA genes, we screened the 11 coding exons and exon-intron boundaries of ERCC4 in 1573 index cases from high-risk Spanish familial breast and ovarian cancer pedigrees that had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The frequency of ERCC4 mutation carriers does not differ between cases and controls, suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported for FANCA, whereas there are approximately 100-fold more FA-A than FA-Q patients, indicating that most biallelic combinations of ERCC4 mutations are embryo lethal. Finally, we identified additional bone-fide FA ERCC4 mutations specifically disrupting interstrand cross-link repair. This article is protected by copyright. All rights reserved.
    Human Mutation 09/2013; · 5.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND PURPOSE: Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important. MATERIALS AND METHODS: A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. RESULTS: rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10(-8) and 6.9×10(-7) respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers' d=5.0×10(-12) in the replication cohort). CONCLUSIONS: This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified.
    Radiotherapy and Oncology 05/2013; · 4.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The term autosomal recessive congenital ichthyosis (ARCI) refers to a group of rare disorders of keratinization classified as nonsyndromic forms of ichthyosis. This group was traditionally divided into lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE) but today it also includes harlequin ichthyosis, self-healing collodion baby, acral self-healing collodion baby, and bathing suit ichthyosis.The combined prevalence of LI and CIE has been estimated at 1 case per 138 000 to 300 000 population. In some countries or regions, such as Norway and the coast of Galicia, the prevalence may be higher due to founder effects. ARCI is genetically highly heterogeneous and has been associated with 6 genes to date: TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22, and ABCA12. In this article, we review the current knowledge on ARCI, with a focus on clinical, histological, ultrastructural, genetic, molecular, and treatment-related aspects.
    Actas Dermo-Sifiliográficas 05/2013; 104(4):270–284.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: On June 22, 2012 the First Symposium of Ichthyosis Experts in Spain was held at the Hospital Niño de Jesús in Madrid. It was a one-day symposium for dermatologists, pediatricians, and physicians-in-training interested in this disease, as well as for other health care professionals involved in the care of patients with ichthyosis. The aim of the meeting was to try to structure the care of ichthyosis patients in Spain. As happens in other rare diseases, because of the low prevalence of ichthyosis and the absence of designated referral centers, the number of patients treated in each center is very low and few dermatologists have any real clinical experience with this condition or know how to order diagnostic genetic tests. This article summarizes the presentations given at the symposium and is intended as a reference for anyone interested in the subject.
    Actas Dermo-Sifiliográficas 01/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Accurate evaluation of unclassified sequence variants in cancer predisposition genes is essential for clinical management and depends on a multifactorial analysis of clinical, genetic, pathologic, and bioinformatic variables and assays of transcript length and abundance. The integrity of assay data in turn relies on appropriate assay design, interpretation, and reporting.METHODS: We conducted a multicenter investigation to compare mRNA splicing assay protocols used by members of the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) consortium. We compared similarities and differences in results derived from analysis of a panel of breast cancer 1, early onset (BRCA1) and breast cancer 2, early onset (BRCA2) gene variants known to alter splicing (BRCA1: c.135-1G>T, c.591C>T, c.594-2A>C, c.671-2A>G, and c.5467+5G>C and BRCA2: c.426-12_8delGTTTT, c.7988A>T, c.8632+1G>A, and c.9501+3A>T). Differences in protocols were then assessed to determine which elements were critical in reliable assay design.RESULTS: PCR primer design strategies, PCR conditions, and product detection methods, combined with a prior knowledge of expected alternative transcripts, were the key factors for accurate splicing assay results. For example, because of the position of primers and PCR extension times, several isoforms associated with BRCA1, c.594-2A>C and c.671-2A>G, were not detected by many sites. Variation was most evident for the detection of low-abundance transcripts (e.g., BRCA2 c.8632+1G>A Delta19,20 and BRCA1 c.135-1G>T Delta5q and Delta3). Detection of low-abundance transcripts was sometimes addressed by using more analytically sensitive detection methods (e.g., BRCA2 c.426-12_8delGTTTT ins18bp).CONCLUSIONS: We provide recommendations for best practice and raise key issues to consider when designing mRNA assays for evaluation of unclassified sequence variants.
    Clin Chem. 01/2013;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In agreement with historical documentation, several genetic studies have revealed ancestral links between the European Romani and India. The entire mitochondrial DNA (mtDNA) of 27 Spanish Romani was sequenced in order to shed further light on the origins of this population. The data were analyzed together with a large published dataset (mainly hypervariable region I [HVS-I] haplotypes) of Romani (N = 1,353) and non-Romani worldwide populations (N>150,000). Analysis of mitogenomes allowed the characterization of various Romani-specific clades. M5a1b1a1 is the most distinctive European Romani haplogroup; it is present in all Romani groups at variable frequencies (with only sporadic findings in non-Romani) and represents 18% of their mtDNA pool. Its phylogeographic features indicate that M5a1b1a1 originated 1.5 thousand years ago (kya; 95% CI: 1.3-1.8) in a proto-Romani population living in Northwest India. U3 represents the most characteristic Romani haplogroup of European/Near Eastern origin (12.4%); it appears at dissimilar frequencies across the continent (Iberia: ∼31%; Eastern/Central Europe: ∼13%). All U3 mitogenomes of our Iberian Romani sample fall within a new sub-clade, U3b1c, which can be dated to 0.5 kya (95% CI: 0.3-0.7); therefore, signaling a lower bound for the founder event that followed admixture in Europe/Near East. Other minor European/Near Eastern haplogroups (e.g. H24, H88a) were also assimilated into the Romani by introgression with neighboring populations during their diaspora into Europe; yet some show a differentiation from the phylogenetically closest non-Romani counterpart. The phylogeny of Romani mitogenomes shows clear signatures of low effective population sizes and founder effects. Overall, these results are in good agreement with historical documentation, suggesting that cultural identity and relative isolation have allowed the Romani to preserve a distinctive mtDNA heritage, with some features linking them unequivocally to their ancestral Indian homeland.
    PLoS ONE 01/2013; 8(10):e75397. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: On June 22, 2012 the First Symposium of Ichthyosis Experts in Spain was held at the Hospital Niño de Jesús in Madrid. It was a one-day symposium for dermatologists, pediatricians, and physicians-in-training interested in this disease, as well as for other health care professionals involved in the care of patients with ichthyosis. The aim of the meeting was to try to structure the care of ichthyosis patients in Spain. As happens in other rare diseases, because of the low prevalence of ichthyosis and the absence of designated referral centers, the number of patients treated in each center is very low and few dermatologists have any real clinical experience with this condition or know how to order diagnostic genetic tests. This article summarizes the presentations given at the symposium and is intended as a reference for anyone interested in the subject.
    Actas Dermo-Sifiliográficas 01/2013; 104(10):877–882.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer and 3-4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer. 132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification. Two PALB2 truncating mutations, the c.1653T>A (p.Tyr551Stop) previously reported, and c.3362del (p.Gly1121ValfsX3) which is a novel frameshift mutation, were identified. Moreover, several PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%. The prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s) involved in the development of breast/pancreatic cancer families is required.
    PLoS ONE 01/2013; 8(7):e67538. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Splicing assays are commonly undertaken in the clinical setting to assess the clinical relevance of sequence variants in disease predisposition genes. A 5-tier classification system incorporating both bioinformatic and splicing assay information was previously proposed as a method to provide consistent clinical classification of such variants. Members of the ENIGMA Consortium Splicing Working Group undertook a study to assess the applicability of the scheme to published assay results, and the consistency of classifications across multiple reviewers. Splicing assay data was identified for 235 BRCA1 and 176 BRCA2 unique variants, from 77 publications. At least six independent reviewers from research and/or clinical settings comprehensively examined splicing assay methods and data reported for 22 variant assays of 21 variants in four publications, and classified the variants using the 5-tier classification scheme. Inconsistencies in variant classification occurred between reviewers for 17 of the variant assays. These could be attributed to a combination of ambiguity in presentation of the classification criteria, differences in interpretation of the data provided, non-standardised reporting of results, and the lack of quantitative data for the aberrant transcripts. We propose suggestions for minimum reporting guidelines for splicing assays, and improvements to the 5-tier splicing classification system to allow future evaluation of its performance as a clinical tool. This article is protected by copyright. All rights reserved.
    Human Mutation 01/2013; · 5.21 Impact Factor

Publication Stats

1k Citations
353.70 Total Impact Points

Institutions

  • 2013
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 2003–2013
    • Centro Nacional de Investigaciones Oncológicas
      • Human Cancer Genetics Programme
      Madrid, Madrid, Spain
    • Port of Spain General Hospital
      City of Port-of-Spain, City of Port of Spain, Trinidad and Tobago
  • 2011–2012
    • Complejo Hospitalario Universitario de Santiago
      • Nursing Department
      Santiago de Compostela, Galicia, Spain
    • Odense University Hospital
      • Department of Clinical Genetics
      Odense, South Denmark, Denmark
  • 2009–2011
    • Instituto Português de Oncologia
      • Department of Pathology
      Oporto, Porto, Portugal
  • 2000–2010
    • University of Santiago de Compostela
      • • Group of Genomic Medicine
      • • Instituto de Medicina Legal
      Santiago, Galicia, Spain
  • 2008
    • Instituto De Medicina Legal
      La Habana, Ciudad de La Habana, Cuba
  • 2006
    • Conselleria de Sanidade
      La Corogne, Galicia, Spain
  • 2001
    • Complejo Hospitalario de Pontevedra
      Pontevedra, Galicia, Spain