Abstract
Leukodystrophies are genetic disorders leading to progressive white matter degeneration in the central nervous system. Mitochondrial aminoacyl tRNA synthase protein is encoded by the nuclear gene AARS2. An autosomal recessive mutation in this gene has been linked to AARS2 mutation-related adult-onset leukodystrophy (AARS2-L) or infantile mitochondrial cardiomyopathy. To date, only 16 AARS2-L cases have been reported in English literature. Thus, the clinical and genetic characteristics of this disease remain to be defined. Through whole-exome sequencing, we identified a Chinese patient with leukodystrophy related to two novel compounds heterozygous mutation in AARS2 (c.965 G > A, p.R322H; c.334 G > C, p.G112R). These two compounds heterozygous variants in AARS2 gene co-segregated with disease in his family. And pyramidal tracts in the spinal cord were involved. Our findings have important implications on genetic counseling for any case with leukodystrophy and extend the mutational spectrum in AARS2 gene.
References
Dec 29, 2000·Journal of Neurology·N Baumann, J C Turpin
Mar 23, 2005·Biochemistry·Luc BonnefondMarie Sissler
May 10, 2011·American Journal of Human Genetics·Alexandra GötzAnu Suomalainen
Jan 27, 2012·Science Translational Medicine·Sarah E CalvoVamsi K Mootha
May 9, 2014·Neurology·Cristina DallabonaMarjo S van der Knaap
Jul 25, 2014·JAMA : the Journal of the American Medical Association·Robert W TaylorPatrick F Chinnery
Feb 7, 2015·Molecular Genetics and Metabolism·Sumit ParikhUNKNOWN GLIA Consortium
Feb 24, 2015·Frontiers in Genetics·Liliya EuroHenna Tyynismaa
May 10, 2016·Annals of Neurology·Adeline VanderverRyan J Taft
Oct 26, 2016·Journal of Human Genetics·Mio HamataniToshiyuki Yamamoto
Oct 14, 2016·Journal of Human Genetics·Laszlo SzpisjakPeter Klivenyi
Oct 18, 2016·JAMA Neurology·David S LynchHenry Houlden
Mar 1, 2017·Neurology. Genetics·Rahul LakshmananIndran Davagnanam
Mar 23, 2017·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J-M LeeB Jeon
Mar 24, 2017·Brain : a Journal of Neurology·David S LynchHenry Houlden
Apr 19, 2018·Journal of Human Genetics·Qing DongZheng-Qi Lu