Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Functional characterization of BRCA1 gene variants by mini-gene splicing assay

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Haploinsufficiency of ARHGAP42 is associated with hypertension

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Global State of the Genetic Counseling Profession

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. Educational delay and attainment in persons with neurofibromatosis 1 in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Breast cancer survival in Nordic BRCA2 mutation carriers-unconventional association with oestrogen receptor status

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Induction of PIK3CA alterations during neoadjuvant letrozole may improve outcome in postmenopausal breast cancer patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Polycystic ovary syndrome and offspring risk of congenital heart defects: a nationwide cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Mutational screening of the breast cancer susceptibility gene BRCA1 leads to the identification of numerous pathogenic variants such as frameshift and nonsense variants, as well as large genomic rearrangements. The screening moreover identifies a large number of variants, for example, missense, silent, and intron variants, which are classified as variants of unknown clinical significance owing to the lack of causal evidence. Variants of unknown clinical significance can potentially have an impact on splicing and therefore functional examinations are warranted to classify whether these variants are pathogenic or benign. Here we validate a mini-gene splicing assay by comparing the results of 24 variants with previously published data from RT-PCR analysis on RNA from blood samples/lymphoblastoid cell lines. The analysis showed an overall concordance of 100%. In addition, we investigated 13 BRCA1 variants of unknown clinical significance or putative variants affecting splicing by in silico analysis and mini-gene splicing assay. Both the in silico analysis and mini-gene splicing assay classified six BRCA1 variants as pathogenic (c.80+1G>A, c.132C>T (p.=), c.213-1G>A, c.670+1delG, c.4185+1G>A, and c.5075-1G>C), whereas six BRCA1 variants were classified as neutral (c.-19-22_-19-21dupAT, c.302-15C>G, c.547+14delG, c.4676-20A>G, c.4987-21G>T, and c.5278-14C>G) and one BRCA1 variant remained unclassified (c.670+16G>A). In conclusion, our study emphasizes that in silico analysis and mini-gene splicing assays are important for the classification of variants, especially if no RNA is available from the patient. This knowledge is crucial for proper genetic counseling of patients and their family members.

OriginalsprogEngelsk
TidsskriftEuropean journal of human genetics : EJHG
Vol/bind22
Udgave nummer12
Sider (fra-til)1362-8
Antal sider7
ISSN1018-4813
DOI
StatusUdgivet - dec. 2014

ID: 44844094