Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4

American Journal of Human Genetics
Jose BrasRita Guerreiro

Abstract

Hereditary autosomal-recessive cerebellar ataxias are a genetically and clinically heterogeneous group of disorders. We used homozygosity mapping and exome sequencing to study a cohort of nine Portuguese families who were identified during a nationwide, population-based, systematic survey as displaying a consistent phenotype of recessive ataxia with oculomotor apraxia (AOA). The integration of data from these analyses led to the identification of the same homozygous PNKP (polynucleotide kinase 3'-phosphatase) mutation, c.1123G>T (p.Gly375Trp), in three of the studied families. When analyzing this particular gene in the exome sequencing data from the remaining cohort, we identified homozygous or compound-heterozygous mutations in five other families. PNKP is a dual-function enzyme with a key role in different pathways of DNA-damage repair. Mutations in this gene have previously been associated with an autosomal-recessive syndrome characterized by microcephaly; early-onset, intractable seizures; and developmental delay (MCSZ). The finding of PNKP mutations associated with recessive AOA extends the phenotype associated with this gene and identifies a fourth locus that causes AOA. These data confirm that MCSZ and some forms of atax...Continue Reading

References

Sep 25, 2003·Brain : a Journal of Neurology·Isabelle Le BerAlexandra Dürr
Jan 23, 2004·Brain : a Journal of Neurology·Isabelle Le BerAlexandra Dürr
Feb 11, 2004·Nature Genetics·Maria-Céu MoreiraMichel Koenig
Mar 8, 2005·Molecular Cell·Nina K BernsteinJ N Mark Glover
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Dec 8, 2009·DNA Repair·James R WhitesideSarah L Allinson
Feb 2, 2010·Nature Genetics·Jun ShenChristopher A Walsh
Jun 29, 2010·FEBS Letters·Frederick A Derheimer, Michael B Kastan
Mar 1, 2011·Trends in Biochemical Sciences·Michael WeinfeldJ N Mark Glover
Nov 9, 2011·Human Mutation·Nada Al TassanSaeed Bohlega
Dec 12, 2012·Neurogenetics·Cathryn PoultonGrazia M S Mancini

❮ Previous
Next ❯

Citations

Mar 5, 2016·Neural Plasticity·Laura NarcisoEugenia Dogliotti
Apr 12, 2016·Neurology. Genetics·Martin PaucarAnn Nordgren
Apr 12, 2016·Neurology. Genetics·José Luiz PedrosoFernando Kok
Mar 13, 2016·Movement Disorders : Official Journal of the Movement Disorder Society·Bettina Balint, Kailash P Bhatia
May 28, 2016·American Journal of Medical Genetics. Part a·Pratibha NairFatma Bastaki
Apr 5, 2016·Annals of Neurology·Conceição BettencourtLesley Jones
Jul 30, 2016·Mechanisms of Ageing and Development·Bingcheng JiangMichael Weinfeld
Jul 28, 2016·Neurología : publicación oficial de la Sociedad Española de Neurología·M Arias
Apr 30, 2016·Mechanisms of Ageing and Development·Lavinia C Dumitrache, Peter J McKinnon
Mar 10, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Christos Ganos, Jose Bras
May 30, 2017·Journal of Neurogenetics·Nicoline SchiessAyman W El-Hattab
Dec 22, 2016·Nature·Nicolas C HochKeith W Caldecott
Dec 8, 2017·Practical Neurology·Tahira N ChoudryHenry Houlden
May 15, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Malco RossiUNKNOWN International Parkinson and Movement Disorder Society Task Force on Classification and Nomenclature of Genetic Movement Diso
Aug 29, 2018·The FEBS Journal·Wai Yan YauNicholas W Wood
Apr 18, 2019·Open Biology·Luca PalazzoIvan Ahel
Nov 7, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jorge Diogo Da SilvaPatrícia Maciel
Jan 21, 2018·Neurology·Elizabeth A Coon, Eduardo E Benarroch
Jun 7, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Stefano C PrevitaliAlessandra Bolino
Sep 21, 2019·Nature Reviews. Disease Primers·A Malcolm R TaylorGrant S Stewart
Sep 24, 2020·Expert Opinion on Therapeutic Targets·Andreia Neves-CarvalhoPatrícia Maciel
Aug 3, 2017·Genes & Development·Peter J McKinnon
Oct 27, 2018·Movement Disorders Clinical Practice·Malco RossiMarcelo Merello
Aug 1, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·T MaiuriR Truant
Jan 14, 2020·Genetics and Molecular Biology·Nicolas C Hoch, Luis M Polo
Aug 18, 2018·Cellular and Molecular Life Sciences : CMLS·Federico T BianchiFerdinando Di Cunto
Feb 9, 2018·Disease Models & Mechanisms·Thomas H Massey, Lesley Jones
May 22, 2019·Translational Neurodegeneration·Luis Bermúdez-Guzmán, Alejandro Leal
Mar 3, 2017·Cerebellum & Ataxias·Marie BeaudinNicolas Dupré
May 2, 2019·Neurology. Genetics·Ilona KalasovaKeith W Caldecott
Apr 14, 2018·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·G E RudenskayaF A Konovalov
Nov 22, 2019·Journal of Cell Communication and Signaling·Madhusoodanan Urulangodi, Abhishek Mohanty

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
genotyping
PCR

Software Mentioned

Burrows Aligner
Genome Analysis Toolkit
Picard
Sequencher
Illumina GenomeStudio
PLINK
PolyPhen

Related Concepts

Related Feeds

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.