转运RNA剪接内切核酸酶突变导致脑桥小脑发育不全。

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

作者信息

Budde Birgit S, Namavar Yasmin, Barth Peter G, Poll-The Bwee Tien, Nürnberg Gudrun, Becker Christian, van Ruissen Fred, Weterman Marian A J, Fluiter Kees, te Beek Erik T, Aronica Eleonora, van der Knaap Marjo S, Höhne Wolfgang, Toliat Mohammad Reza, Crow Yanick J, Steinling Maja, Voit Thomas, Roelenso Filip, Brussel Wim, Brockmann Knut, Kyllerman Marten, Boltshauser Eugen, Hammersen Gerhard, Willemsen Michèl, Basel-Vanagaite Lina, Krägeloh-Mann Ingeborg, de Vries Linda S, Sztriha Laszlo, Muntoni Francesco, Ferrie Colin D, Battini Roberta, Hennekam Raoul C M, Grillo Eugenio, Beemer Frits A, Stoets Loes M E, Wollnik Bernd, Nürnberg Peter, Baas Frank

机构信息

Cologne Center for Genomics and Institute for Genetics, University of Cologne, Cologne, Germany.

出版信息

Nat Genet. 2008 Sep;40(9):1113-8. doi: 10.1038/ng.204.

DOI:10.1038/ng.204

PMID:18711368

Abstract

Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.

摘要

桥脑小脑发育不全（PCH）是一组常染色体隐性神经退行性疾病，其发病于产前，有小脑萎缩或发育不全、腹侧桥脑发育不全、小头畸形、不同程度的新皮质萎缩以及严重的智力和运动障碍。在两种亚型，即PCH2和PCH4中，我们在tRNA剪接内切核酸酶复合体的四个不同亚基中的三个中发现了突变。我们的研究结果表明RNA加工是神经疾病中一种新的基本细胞损伤。