SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Klein Reinhard)
 

Sökning: WFRF:(Klein Reinhard) > (2015-2019) > Rare Variants in MM...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004437naa a2200661 4500
001oai:DiVA.org:umu-127970
003SwePub
008161121s2016 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1279702 URI
0247 a https://doi.org/10.1016/j.ajhg.2016.07.0082 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Auer-Grumbach, Michaela4 aut
2451 0a Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies
264 1b Elsevier BV,c 2016
338 a print2 rdacarrier
520 a Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade beta-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
7001 a Toegel, Stefan4 aut
7001 a Schabhuettl, Maria4 aut
7001 a Weinmann, Daniela4 aut
7001 a Chiari, Catharina4 aut
7001 a Bennett, David L. H.4 aut
7001 a Beetz, Christian4 aut
7001 a Klein, Dennis4 aut
7001 a Andersen, Peter M.u Umeå universitet,Klinisk neurovetenskap4 aut0 (Swepub:umu)pean0001
7001 a Boehme, Ilka4 aut
7001 a Fink-Puches, Regina4 aut
7001 a Gonzalez, Michael4 aut
7001 a Harms, Matthew B.4 aut
7001 a Motley, William4 aut
7001 a Reilly, Mary M.4 aut
7001 a Renner, Wilfried4 aut
7001 a Rudnik-Schoeneborn, Sabine4 aut
7001 a Schlotter-Weigel, Beate4 aut
7001 a Themistocleous, Andreas C.4 aut
7001 a Weishaupt, Jochen H.4 aut
7001 a Ludolph, Albert C.4 aut
7001 a Wieland, Thomas4 aut
7001 a Tao, Feifei4 aut
7001 a Abreu, Lisa4 aut
7001 a Windhager, Reinhard4 aut
7001 a Zitzelsberger, Manuela4 aut
7001 a Strom, Tim M.4 aut
7001 a Walther, Thomas4 aut
7001 a Scherer, Steven S.4 aut
7001 a Zuchner, Stephan4 aut
7001 a Martini, Rudolf4 aut
7001 a Senderek, Jan4 aut
7102 a Umeå universitetb Klinisk neurovetenskap4 org
7730 t American Journal of Human Geneticsd : Elsevier BVg 99:3, s. 607-623q 99:3<607-623x 0002-9297x 1537-6605
8564 u http://www.cell.com/article/S0002929716302828/pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127970
8564 8u https://doi.org/10.1016/j.ajhg.2016.07.008

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy