TY  - JOUR
A1  - Neuhoff, Nina
A1  - Bruder, Jennifer
A1  - Bartling, Jürgen
A1  - Warnke, Andreas
A1  - Remschmidt, Helmut
A1  - Müller-Myhsok, Bertram
A1  - Schulte-Körne, Gerd
T1  - Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia
JF  - PLoS One
N2  - Dyslexia affects 5-10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected'' despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/ contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia.
KW  - processing deficits
KW  - children
KW  - event-related potentials
KW  - mismatch negativity mmn
KW  - developmental dyslexia
KW  - reading disability
KW  - auditory discrimination
KW  - susceptibility gene
KW  - speech perception
KW  - novelty detection
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133686
VL  - 7
IS  - 5
ER  - 
TY  - JOUR
A1  - Fernández-Rodríguez, Juana
A1  - Quiles, Francisco
A1  - Blanco, Ignacio
A1  - Teulé, Alex
A1  - Feliubadaló, Lídia
A1  - del Valle, Jesús
A1  - Salinas, Mónica
A1  - Izquierdo, Ángel
A1  - Darder, Esther
A1  - Schindler, Detlev
A1  - Capellá, Gabriel
A1  - Brunet, Joan
A1  - Lázaro, Conxi
A1  - Angel Pujana, Miguel
T1  - Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families
JF  - BMC Cancer
N2  - Background: Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results. 
Methods: The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations. 
Results: This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them. Conclusions: Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.
KW  - SLX4
KW  - Holliday junction reolvass
KW  - Fanconi-anemia subtype
KW  - susceptibility gene
KW  - helicase BRIP1
KW  - ovarian cancer
KW  - DNA repair
KW  - mutations
KW  - protein
KW  - RAD51C
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131772
VL  - 12
IS  - 84
ER  -