Sökning: WFRF:(Levy Lahad Ephrat) > Mitochondrial PITRM...
Fältnamn | Indikatorer | Metadata |
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000 | 04243naa a2200565 4500 | |
001 | oai:DiVA.org:su-166869 | |
003 | SwePub | |
008 | 190306s2018 | |||||||||||000 ||eng| | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1668692 URI |
024 | 7 | a https://doi.org/10.1136/jmedgenet-2018-1053302 DOI |
040 | a (SwePub)su | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Langer, Yeshaya4 aut |
245 | 1 0 | a Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar atrophy |
264 | c 2018-05-15 | |
264 | 1 | b BMJ,c 2018 |
338 | a print2 rdacarrier | |
520 | a Objective To identify the genetic basis of a childhood-onset syndrome of variable severity characterised by progressive spinocerebellar ataxia, mental retardation, psychotic episodes and cerebellar atrophy. Methods Identification of the underlying mutations by whole exome and whole genome sequencing. Consequences were examined in patients' cells and in yeast. Results Two brothers from a consanguineous Palestinian family presented with progressive spinocerebellar ataxia, mental retardation and psychotic episodes. Serial brain imaging showed severe progressive cerebellar atrophy. Whole exome sequencing revealed a novel mutation: pitrilysin metallopeptidase 1 (PITRM1) c.2795C>T, p.T931M, homozygous in the affected children and resulting in 95% reduction in PITRM1 protein. Whole genome sequencing revealed a chromosome X structural rearrangement that also segregated with the disease. Independently, two siblings from a second Palestinian family presented with similar, somewhat milder symptoms and the same PITRM1 mutation on a shared haplotype. PITRM1T931M carrier frequency was 0.027 (3/110) in the village of the first family evaluated, and 0/300 among Palestinians from other locales. PITRM1 is a mitochondrial matrix enzyme that degrades 10-65 amino acid oligopeptides, including the mitochondrial fraction of amyloid-beta peptide. Analysis of peptide cleavage activity by the PITRM1T931M protein revealed a significant decrease in the degradation capacity specifically of peptides >= 40 amino acids. Conclusion PITRM1T931M results in childhood-onset recessive cerebellar pathology. Severity of PITRM1-related disease may be affected by the degree of impairment in cleavage of mitochondrial long peptides. Disruption and deletion of X linked regulatory segments may also contribute to severity. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
700 | 1 | a Aran, Adi4 aut |
700 | 1 | a Gulsuner, Suleyman4 aut |
700 | 1 | a Abu Libdeh, Bassam4 aut |
700 | 1 | a Renbaum, Paul4 aut |
700 | 1 | a Brunetti, Dario4 aut |
700 | 1 | a Teixeira, Pedro-Filipeu Stockholms universitet,Institutionen för biokemi och biofysik4 aut0 (Swepub:su)pete5877 |
700 | 1 | a Walsh, Tom4 aut |
700 | 1 | a Zeligson, Sharon4 aut |
700 | 1 | a Ruotolo, Roberta4 aut |
700 | 1 | a Beeri, Rachel4 aut |
700 | 1 | a Dweikat, Imad4 aut |
700 | 1 | a Shahrour, Maher4 aut |
700 | 1 | a Weinberg-Shukron, Ariella4 aut |
700 | 1 | a Zandeh, Fouad4 aut |
700 | 1 | a Baruffini, Enrico4 aut |
700 | 1 | a Glaser, Elzbietau Stockholms universitet,Institutionen för biokemi och biofysik4 aut0 (Swepub:su)glase |
700 | 1 | a King, Mary-Claire4 aut |
700 | 1 | a Levy-Lahad, Ephrat4 aut |
700 | 1 | a Zeviani, Massimo4 aut |
700 | 1 | a Segel, Reeval4 aut |
710 | 2 | a Stockholms universitetb Institutionen för biokemi och biofysik4 org |
773 | 0 | t Journal of Medical Geneticsd : BMJg 55:9, s. 599-606q 55:9<599-606x 0022-2593x 1468-6244 |
856 | 4 | u https://www.repository.cam.ac.uk/handle/1810/285560 |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-166869 |
856 | 4 8 | u https://doi.org/10.1136/jmedgenet-2018-105330 |
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