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Sökning: onr:"swepub:oai:DiVA.org:umu-151563" > Comprehensive analy...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004181naa a2200637 4500
001oai:DiVA.org:umu-151563
003SwePub
008180910s2018 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1515632 URI
0247 a https://doi.org/10.1136/jnnp-2017-3176112 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Mueller, Kathrin4 aut
2451 0a Comprehensive analysis of the mutation spectrum in 301 German ALS families
264 c 2018-04-12
264 1b BMJ Publishing Group Ltd,c 2018
338 a print2 rdacarrier
520 a Objectives Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.Methods Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.Results 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.Conclusions We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
7001 a Brenner, David4 aut
7001 a Weydt, Patrick4 aut
7001 a Meyer, Thomas4 aut
7001 a Grehl, Torsten4 aut
7001 a Petri, Susanne4 aut
7001 a Grosskreutz, Julian4 aut
7001 a Schuster, Joachim4 aut
7001 a Volk, Alexander E.4 aut
7001 a Borck, Guntram4 aut
7001 a Kubisch, Christian4 aut
7001 a Klopstock, Thomas4 aut
7001 a Zeller, Daniel4 aut
7001 a Jablonka, Sibylle4 aut
7001 a Sendtner, Michael4 aut
7001 a Klebe, Stephan4 aut
7001 a Knehr, Antje4 aut
7001 a Guenther, Kornelia4 aut
7001 a Weis, Joachim4 aut
7001 a Claeys, Kristl G.4 aut
7001 a Schrank, Berthold4 aut
7001 a Sperfeld, Anne-Dorte4 aut
7001 a Huebers, Annemarie4 aut
7001 a Otto, Markus4 aut
7001 a Dorst, Johannes4 aut
7001 a Meitinger, Thomas4 aut
7001 a Strom, Tim M.4 aut
7001 a Andersen, Peter M.,d 1962-u Umeå universitet,Klinisk neurovetenskap,Department of Neurology, Ulm University, Ulm, Germany4 aut0 (Swepub:umu)pean0001
7001 a Ludolph, Albert C.4 aut
7001 a Weishaupt, Jochen H.4 aut
7102 a Umeå universitetb Klinisk neurovetenskap4 org
7730 t Journal of Neurology, Neurosurgery and Psychiatryd : BMJ Publishing Group Ltdg 89:8, s. 817-827q 89:8<817-827x 0022-3050x 1468-330X
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-151563
8564 8u https://doi.org/10.1136/jnnp-2017-317611

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