Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9

European Journal of Human Genetics : EJHG
Fanny KortümKerstin Kutsche

Abstract

Pontocerebellar hypoplasia (PCH) represents a group of autosomal-recessive progressive neurodegenerative disorders of prenatal onset. Eleven PCH subtypes are classified according to clinical, neuroimaging and genetic findings. Individuals with PCH type 9 (PCH9) have a unique combination of postnatal microcephaly, hypoplastic cerebellum and pons, and hypoplastic or absent corpus callosum. PCH9 is caused by biallelic variants in AMPD2 encoding adenosine monophosphate deaminase 2; however, a homozygous AMPD2 frameshift variant has recently been reported in two family members with spastic paraplegia type 63 (SPG63). We identified homozygous or compound heterozygous AMPD2 variants in eight PCH-affected individuals from six families. The eight variants likely affect function and comprise one frameshift, one nonsense and six missense variants; seven of which were novel. The main clinical manifestations in the eight new patients and 17 previously reported individuals with biallelic AMPD2 variants were postnatal microcephaly, severe global developmental delay, spasticity, and central visual impairment. Brain imaging data identified hypomyelination, hypoplasia of the cerebellum and pons, atrophy of the cerebral cortex, complete or partia...Continue Reading

References

Aug 20, 1995·Archives of Biochemistry and Biophysics·M T Bausch-Jurken, R L Sabina
May 15, 2003·Biochemical and Biophysical Research Communications·Amy Louise Haas, Richard L Sabina
Aug 20, 2008·Nature Genetics·Birgit S BuddeFrank Baas
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Oct 6, 2010·American Journal of Human Genetics·Orly AgamyOhad S Birk
Oct 19, 2010·Brain : a Journal of Neurology·Yasmin NamavarBwee Tien Poll-The
Jun 10, 2011·Bioinformatics·Petr DanecekUNKNOWN 1000 Genomes Project Analysis Group
Jan 4, 2012·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Keiko ToyamaTakayuki Morisaki
Oct 2, 2012·Nature Genetics·Ganeshwaran H MochidaChristopher A Walsh
Jan 4, 2013·Neurology·Sabine Rudnik-SchönebornKlaus Zerres
Feb 15, 2014·Orphanet Journal of Rare Diseases·Veerle Rc EggensFrank Baas
Jun 14, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Sabine Rudnik-SchönebornKlaus Zerres
Jul 26, 2014·Science·Jennifer C Darnell
Aug 26, 2014·Journal of Neurology·Ayelet HalevyAlexander Lossos
Oct 31, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kelly D FarwellSha Tang
Nov 2, 2014·Lipids in Health and Disease·Joan HelmeringDavid J Lloyd
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Sep 19, 2015·Scientific Reports·Yunfei GuoKai Wang
Dec 17, 2015·European Journal of Human Genetics : EJHG·Katta Mohan GirishaKerstin Kutsche
Jan 5, 2016·Nature Reviews. Molecular Cell Biology·Cornelia KilchertLidia Vasiljeva
Mar 5, 2016·Human Mutation·Johan T den DunnenPeter E M Taschner
Apr 12, 2016·Neurology. Genetics·Ashley P L MarshPaul J Lockhart
May 10, 2016·Annals of Neurology·Adeline VanderverRyan J Taft
Nov 17, 2016·European Journal of Human Genetics : EJHG·Daniel TrujillanoRami Abou Jamra
Feb 9, 2017·American Journal of Medical Genetics. Part a·Ashley P L MarshPaul J Lockhart
Aug 18, 2017·Neurology. Genetics·Andrea AccogliFederico Zara
Aug 22, 2017·American Journal of Human Genetics·Isaac Marin-ValenciaJoseph G Gleeson
Aug 22, 2017·American Journal of Human Genetics·Ekaterina L IvanovaJamel Chelly
Nov 3, 2017·Neuron·Mridu KapurSusan L Ackerman

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Citations

Oct 27, 2018·Purinergic Signalling·Lars Petter Jordheim
May 16, 2020·The Cerebellum·Christina T RüschEugen Boltshauser
Aug 15, 2019·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Klaus DieterichJudith G Hall
Dec 14, 2019·American Journal of Medical Genetics. Part a·Nicolas J AbreuMegan A Waldrop
Aug 10, 2018·European Journal of Human Genetics : EJHG·Ashley P L MarshRichard J Leventer
Nov 27, 2019·European Journal of Medical Genetics·Pascale Saugier-VeberAnnie Laquerrière
Feb 4, 2021·The Cerebellum·Andrea AccogliMyriam Srour
Jun 1, 2021·Frontiers in Pharmacology·Mercedes Garcia-GilMaria Grazia Tozzi
Dec 24, 2021·Journal of Child Neurology·Nihaal ReddyKshitij Mankad

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Methods Mentioned

BETA
deamination

Software Mentioned

Genome Analysis Toolkit ( GATK )
AnnoVar
Sequence Pilot
SeqMule
gnomAD browser

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