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Sökning: onr:"swepub:oai:DiVA.org:su-166869" > Mitochondrial PITRM...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004243naa a2200565 4500
001oai:DiVA.org:su-166869
003SwePub
008190306s2018 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1668692 URI
0247 a https://doi.org/10.1136/jmedgenet-2018-1053302 DOI
040 a (SwePub)su
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Langer, Yeshaya4 aut
2451 0a Mitochondrial PITRM1 peptidase loss-of-function in childhood cerebellar atrophy
264 c 2018-05-15
264 1b 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 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
650 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
7001 a Aran, Adi4 aut
7001 a Gulsuner, Suleyman4 aut
7001 a Abu Libdeh, Bassam4 aut
7001 a Renbaum, Paul4 aut
7001 a Brunetti, Dario4 aut
7001 a Teixeira, Pedro-Filipeu Stockholms universitet,Institutionen för biokemi och biofysik4 aut0 (Swepub:su)pete5877
7001 a Walsh, Tom4 aut
7001 a Zeligson, Sharon4 aut
7001 a Ruotolo, Roberta4 aut
7001 a Beeri, Rachel4 aut
7001 a Dweikat, Imad4 aut
7001 a Shahrour, Maher4 aut
7001 a Weinberg-Shukron, Ariella4 aut
7001 a Zandeh, Fouad4 aut
7001 a Baruffini, Enrico4 aut
7001 a Glaser, Elzbietau Stockholms universitet,Institutionen för biokemi och biofysik4 aut0 (Swepub:su)glase
7001 a King, Mary-Claire4 aut
7001 a Levy-Lahad, Ephrat4 aut
7001 a Zeviani, Massimo4 aut
7001 a Segel, Reeval4 aut
7102 a Stockholms universitetb Institutionen för biokemi och biofysik4 org
7730 t Journal of Medical Geneticsd : BMJg 55:9, s. 599-606q 55:9<599-606x 0022-2593x 1468-6244
8564 u https://www.repository.cam.ac.uk/handle/1810/285560
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-166869
8564 8u https://doi.org/10.1136/jmedgenet-2018-105330

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