| Literature DB >> 26539891 |
Ender Karaca1, Tamar Harel1, Davut Pehlivan1, Shalini N Jhangiani2, Tomasz Gambin1, Zeynep Coban Akdemir1, Claudia Gonzaga-Jauregui3, Serkan Erdin4, Yavuz Bayram1, Ian M Campbell1, Jill V Hunter5, Mehmed M Atik1, Hilde Van Esch6, Bo Yuan1, Wojciech Wiszniewski1, Sedat Isikay7, Gozde Yesil8, Ozge O Yuregir9, Sevcan Tug Bozdogan10, Huseyin Aslan11, Hatip Aydin12, Tulay Tos13, Ayse Aksoy14, Darryl C De Vivo15, Preti Jain16, B Bilge Geckinli17, Ozlem Sezer18, Davut Gul19, Burak Durmaz20, Ozgur Cogulu20, Ferda Ozkinay20, Vehap Topcu21, Sukru Candan22, Alper Han Cebi23, Mevlit Ikbal23, Elif Yilmaz Gulec24, Alper Gezdirici24, Erkan Koparir24, Fatma Ekici24, Salih Coskun25, Salih Cicek26, Kadri Karaer27, Asuman Koparir28, Mehmet Bugrahan Duz28, Emre Kirat28, Elif Fenercioglu28, Hakan Ulucan28, Mehmet Seven28, Tulay Guran29, Nursel Elcioglu30, Mahmut Selman Yildirim31, Dilek Aktas32, Mehmet Alikaşifoğlu32, Mehmet Ture33, Tahsin Yakut33, John D Overton3, Adnan Yuksel34, Mustafa Ozen34, Donna M Muzny2, David R Adams35, Eric Boerwinkle36, Wendy K Chung37, Richard A Gibbs2, James R Lupski38.
Abstract
Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations.Entities:
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Year: 2015 PMID： 26539891 PMCID： PMC4824012 DOI： 10.1016/j.neuron.2015.09.048
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173