TY  - JOUR
A1  - Hopfner, Franziska
A1  - Schormair, Barbara
A1  - Knauf, Franziska
A1  - Berthele, Achim
A1  - Tölle, Thomas R.
A1  - Baron, Ralf
A1  - Maier, Christoph
A1  - Treede, Rolf-Detlef
A1  - Binder, Andreas
A1  - Sommer, Claudia
A1  - Maihöfner, Christian
A1  - Kunz, Wolfram
A1  - Zimprich, Friedrich
A1  - Heemann, Uwe
A1  - Pfeufer, Arne
A1  - Näbauer, Michael
A1  - Kääb, Stefan
A1  - Nowak, Barbara
A1  - Gieger, Christian
A1  - Lichtner, Peter
A1  - Trenkwalder, Claudia
A1  - Oexle, Konrad
A1  - Winkelmann, Juliane
T1  - Novel SCARB2 mutation in Action Myoclonus-Renal Failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features
JF  - BMC Neurology
N2  - Background: 

Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features. 

Methods: 

In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons. 

Results: 

A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA). 

Conclusions: 

Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.
KW  - Demyelinating peripheral neuropathy
KW  - Beta-glucocerebrosidase
KW  - Epilepsy
KW  - LIMP-2
KW  - Mice
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141209
VL  - 11
IS  - 134
ER  - 
TY  - JOUR
A1  - Marenholz, Ingo
A1  - Esparza-Gordillo, Jorge
A1  - Rüschendorf, Franz
A1  - Bauerfeind, Anja
A1  - Strachan, David P.
A1  - Spycher, Ben D.
A1  - Baurecht, Hansjörg
A1  - Magaritte-Jeannin, Patricia
A1  - Sääf, Annika
A1  - Kerkhof, Marjan
A1  - Ege, Markus
A1  - Baltic, Svetlana
A1  - Matheson, Melanie C.
A1  - Li, Jin
A1  - Michel, Sven
A1  - Ang, Wei Q.
A1  - McArdle, Wendy
A1  - Arnold, Andreas
A1  - Homuth, Georg
A1  - Demenais, Florence
A1  - Bouzigon, Emmanuelle
A1  - Söderhäll, Cilla
A1  - Pershagen, Göran
A1  - de Jongste, Johan C.
A1  - Postma, Dirkje S.
A1  - Braun-Fahrländer, Charlotte
A1  - Horak, Elisabeth
A1  - Ogorodova, Ludmila M.
A1  - Puzyrev, Valery P.
A1  - Bragina, Elena Yu
A1  - Hudson, Thomas J.
A1  - Morin, Charles
A1  - Duffy, David L.
A1  - Marks, Guy B.
A1  - Robertson, Colin F.
A1  - Montgomery, Grant W.
A1  - Musk, Bill
A1  - Thompson, Philip J.
A1  - Martin, Nicholas G.
A1  - James, Alan
A1  - Sleiman, Patrick
A1  - Toskala, Elina
A1  - Rodriguez, Elke
A1  - Fölster-Holst, Regina
A1  - Franke, Andre
A1  - Lieb, Wolfgang
A1  - Gieger, Christian
A1  - Heinzmann, Andrea
A1  - Rietschel, Ernst
A1  - Keil, Thomas
A1  - Cichon, Sven
A1  - Nöthen, Markus M.
A1  - Pennel, Craig E.
A1  - Sly, Peter D.
A1  - Schmidt, Carsten O.
A1  - Matanovic, Anja
A1  - Schneider, Valentin
A1  - Heinig, Matthias
A1  - Hübner, Norbert
A1  - Holt, Patrick G.
A1  - Lau, Susanne
A1  - Kabesch, Michael
A1  - Weidinger, Stefan
A1  - Hakonarson, Hakon
A1  - Ferreira, Manuel A. R.
A1  - Laprise, Catherine
A1  - Freidin, Maxim B.
A1  - Genuneit, Jon
A1  - Koppelman, Gerard H.
A1  - Melén, Erik
A1  - Dizier, Marie-Hélène
A1  - Henderson, A. John
A1  - Lee, Young Ae
T1  - Meta-analysis identifies seven susceptibility loci involved in the atopic march
JF  - Nature Communications
N2  - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
KW  - chromosome 11Q13
KW  - risk
KW  - genomewide association
KW  - hay fever
KW  - birth cohort
KW  - filaggrin mutations
KW  - food allergy
KW  - juvenile myoclonic epilepsy
KW  - childhood asthma
KW  - dermatitis
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835
VL  - 6
IS  - 8804
ER  - 
TY  - JOUR
A1  - Dumont, Martine
A1  - Weber-Lassalle, Nana
A1  - Joly-Beauparlant, Charles
A1  - Ernst, Corinna
A1  - Droit, Arnaud
A1  - Feng, Bing-Jian
A1  - Dubois, Stéphane
A1  - Collin-Deschesnes, Annie-Claude
A1  - Soucy, Penny
A1  - Vallée, Maxime
A1  - Fournier, Frédéric
A1  - Lemaçon, Audrey
A1  - Adank, Muriel A.
A1  - Allen, Jamie
A1  - Altmüller, Janine
A1  - Arnold, Norbert
A1  - Ausems, Margreet G. E. M.
A1  - Berutti, Riccardo
A1  - Bolla, Manjeet K.
A1  - Bull, Shelley
A1  - Carvalho, Sara
A1  - Cornelissen, Sten
A1  - Dufault, Michael R.
A1  - Dunning, Alison M.
A1  - Engel, Christoph
A1  - Gehrig, Andrea
A1  - Geurts-Giele, Willemina R. R.
A1  - Gieger, Christian
A1  - Green, Jessica
A1  - Hackmann, Karl
A1  - Helmy, Mohamed
A1  - Hentschel, Julia
A1  - Hogervorst, Frans B. L.
A1  - Hollestelle, Antoinette
A1  - Hooning, Maartje J.
A1  - Horváth, Judit
A1  - Ikram, M. Arfan
A1  - Kaulfuß, Silke
A1  - Keeman, Renske
A1  - Kuang, Da
A1  - Luccarini, Craig
A1  - Maier, Wolfgang
A1  - Martens, John W. M.
A1  - Niederacher, Dieter
A1  - Nürnberg, Peter
A1  - Ott, Claus-Eric
A1  - Peters, Annette
A1  - Pharoah, Paul D. P.
A1  - Ramirez, Alfredo
A1  - Ramser, Juliane
A1  - Riedel-Heller, Steffi
A1  - Schmidt, Gunnar
A1  - Shah, Mitul
A1  - Scherer, Martin
A1  - Stäbler, Antje
A1  - Strom, Tim M.
A1  - Sutter, Christian
A1  - Thiele, Holger
A1  - van Asperen, Christi J.
A1  - van der Kolk, Lizet
A1  - van der Luijt, Rob B.
A1  - Volk, Alexander E.
A1  - Wagner, Michael
A1  - Waisfisz, Quinten
A1  - Wang, Qin
A1  - Wang-Gohrke, Shan
A1  - Weber, Bernhard H. F.
A1  - Devilee, Peter
A1  - Tavtigian, Sean
A1  - Bader, Gary D.
A1  - Meindl, Alfons
A1  - Goldgar, David E.
A1  - Andrulis, Irene L.
A1  - Schmutzler, Rita K.
A1  - Easton, Douglas F.
A1  - Schmidt, Marjanka K.
A1  - Hahnen, Eric
A1  - Simard, Jacques
T1  - Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry
JF  - Cancers
N2  - Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
KW  - breast cancer
KW  - genetic susceptibility
KW  - whole-exome sequencing
KW  - moderate-penetrance genes
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281768
SN  - 2072-6694
VL  - 14
IS  - 14
ER  -