Abstract
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. Identification of the underlying mutations by whole exome and whole genome sequencing. Consequences were examined in patients' cells and in yeast. 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 oligo...Continue Reading
References
Feb 13, 2002·Kennedy Institute of Ethics Journal·UNKNOWN National Reference Center for Bioethics Literature
Apr 17, 2004·Science·Joyce W LustbaderHao Wu
Mar 23, 2006·Human Molecular Genetics·Maria ManczakP Hemachandra Reddy
Oct 20, 2006·Nature·Michael T Lin, M Flint Beal
May 9, 2008·PLoS Computational Biology·Michał J Okoniewski, Crispin J Miller
May 15, 2009·Neurogenetics·M AnheimM Koenig
Oct 31, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Liam TownCarol Wicking
Feb 18, 2011·Genome Research·Alexej AbyzovMark Gerstein
Feb 18, 2012·The New England Journal of Medicine·Mathieu AnheimMichel Koenig
Apr 28, 2012·Genetic Epidemiology·Jianxin Shi, Peng Li
Oct 9, 2012·Free Radical Biology & Medicine·Pedro Filipe TeixeiraElzbieta Glaser
Nov 1, 2013·Nucleic Acids Research·Jeffrey R MacDonaldStephen W Scherer
Feb 21, 2014·The New England Journal of Medicine·Paulina Navon ElkanEphrat Levy-Lahad
Sep 2, 2014·Cell Metabolism·Dirk MossmannChris Meisinger
Oct 12, 2014·Trends in Plant Science·Beata KmiecElzbieta Glaser
Feb 28, 2015·GigaScience·Christopher C ChangJames J Lee
Apr 26, 2015·Methods in Molecular Biology·Pedro F TeixeiraElzbieta Glaser
Dec 10, 2015·Bioinformatics·Xiaoyu ChenChristopher T Saunders
Dec 25, 2015·EMBO Molecular Medicine·Dario BrunettiLaurence A Bindoff
May 11, 2016·Neurology·Adi AranEphrat Levy-Lahad
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Mar 3, 2017·Cerebellum & Ataxias·Marie BeaudinNicolas Dupré
Mar 6, 2017·DNA Repair·Raima Das, Sankar Kumar Ghosh
Feb 1, 2018·Protein Science : a Publication of the Protein Society·Jillian E Smith-Carpenter, Benjamin J Alper
May 24, 2018·Human Mutation·Alex HenrieKaren Eilbeck
Citations
Jul 13, 2018·CNS Neuroscience & Therapeutics·Josef Finsterer, Sinda Zarrouk-Mahjoub
Jun 4, 2020·The FEBS Journal·Cansu KücükköseFriederike-Nora Vögtle
Feb 23, 2020·Annual Review of Biochemistry·Soni DeshwalThomas Langer
Jul 8, 2020·Molecular Psychiatry·María José PérezMichela Deleidi
Aug 28, 2020·Frontiers in Pharmacology·Dario BrunettiAlessandra Valerio
Nov 15, 2020·Pharmaceutics·Emanuela BottaniDario Brunetti
Jan 17, 2021·FEBS Letters·Maria Gomez-Fabra Gala, Friederike-Nora Vögtle
Jan 16, 2021·International Journal of Molecular Sciences·Margarita A SazonovaIgor A Sobenin
Mar 7, 2021·Genes·Camilla Ceccatelli BertiClaudia Donnini
Apr 10, 2021·Human Genetics·Marjo K HytönenHannes Lohi
May 6, 2021·Aging Cell·Fang DuShirley ShiDu Yan
Jun 18, 2021·Journal of Medical Genetics·Deborah TolomeoFilippo M M Santorelli
Aug 7, 2021·Biomedicines·Dario BrunettiMassimo Zeviani
Aug 8, 2021·International Journal of Molecular Sciences·Joseph E FriedlanderHui Feng