Mutations in the palmitoyl-protein thioesterase gene (PPT; CLN1) causing juvenile neuronal ceroid lipofuscinosis with granular osmiophilic deposits

Human Molecular Genetics
H M MitchisonA M O'Rawe

Abstract

A subtype of neuronal ceroid lipofuscinosis (NCL) is well recognized which has a clinical course consistent with juvenile NCL (JNCL) but the ultrastructural characteristics of infantile NCL (INCL): granular osmiophilic deposits (GROD). Evidence supporting linkage of this phenotype, designated vJNCL/GROD, to the INCL region of chromosome 1p32 was demonstrated (pairwise lod score with D1S211 , Z max = 2.63, straight theta = 0.00). The INCL gene, palmitoyl-protein thioesterase (PPT ; CLN1), was therefore screened for mutations in 11 vJNCL/GROD families. Five mutations in the PPT gene were identified: three missense mutations, Thr75Pro, Asp79Gly, Leu219Gln, and two nonsense mutations, Leu10STOP and Arg151STOP. The missense mutation Thr75Pro accounted for nine of the 22 disease chromosomes analysed and the nonsense mutation Arg151STOP for seven. Nine out of 11 patients were shown to combine a missense mutation on one disease chromosome with a nonsense mutation on the other. Mutations previously identified in INCL were not observed in vJNCL/GROD families. Thioesterase activity in peripheral blood lymphoblast cells was found to be markedly reduced in vJNCL/GROD patients compared with controls. These results demonstrate that this subty...Continue Reading

Citations

Feb 6, 2007·Annals of Saudi Medicine·A S Dammas
Aug 10, 2000·Italian Journal of Neurological Sciences·N Nardocci, F Cardona
Jun 10, 2010·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·M N Preising, B Lorenz
Apr 19, 2011·Journal of Inherited Metabolic Disease·María-Socorro Pérez-PoyatoMercè Pineda Marfà
Jul 16, 2004·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Sara Mole
May 29, 2000·Current Opinion in Genetics & Development·L PeltonenJ Vesa
Nov 28, 2001·European Journal of Biochemistry·J M HolopainenI Järvelä
Jul 22, 2011·Human Molecular Genetics·Roshni R SingarajaMichael R Hayden
Mar 30, 2013·Human Molecular Genetics·Jake N MillerDavid A Pearce
Mar 29, 2007·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·R KälviäinenO P van Diggelen
Aug 14, 1999·Epilepsia·S Mole, M Gardiner
Jan 29, 2000·Archives of Disease in Childhood·R Robinson, M Gardiner
Jul 17, 1998·The Journal of Clinical Investigation·A K DasS L Hofmann
Jun 19, 2013·Journal of Pediatric Neurosciences·Arif KhanJayprakash Gosalakkal
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·J J BellizziJ Clardy
Aug 4, 2010·Cellular and Molecular Life Sciences : CMLS·Amanda L Getty, David A Pearce
Oct 2, 2001·American Journal of Medical Genetics·A V Delgado-EscuetaK Yamakawa
Nov 28, 2001·Current Opinion in Neurology·H M Mitchison, S E Mole
Jul 8, 2000·Cell Structure and Function·I McIntoshE W Jab
Nov 1, 2007·Expert Opinion on Medical Diagnostics·Amanda L GettyDavid A Pearce
Apr 12, 2001·Ultrastructural Pathology·R BoldriniC Bosman
Mar 9, 2010·Neurobiology of Disease·Stephanie SajaChristopher A Korey
Mar 24, 2009·Pediatric Neurology·Alessandro SimonatiFilippo M Santorelli
Mar 5, 2004·Brain Pathology·Sara E Mole
Mar 5, 2004·Brain Pathology·Hannah M MitchisonJonathan D Cooper
Oct 13, 2006·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Sara E Mole
May 13, 2015·Biochimica Et Biophysica Acta·Jaime Cárcel-TrullolsDavid A Pearce
May 16, 2015·Biochimica Et Biophysica Acta·Romina KohanInés Noher de Halac
Dec 4, 2012·Biochimica Et Biophysica Acta·Glenn W AndersonAlessandro Simonati

❮ Previous
Next ❯

Related Concepts

Related Feeds

Batten Disease

Batten Disease is a group of nervous system disorders known as neuronal ceroid lipofuscinosis. This feed focuses on neurobiological and neuropathological aspects of this disease.