Abstract
Joubert syndrome (JS) and related disorders (JSRD) are autosomal recessive and X-linked disorders characterized by hypoplasia of the cerebellar vermis with a characteristic ‘molar tooth sign’ on brain imaging and accompanying neurological symptoms including episodic hyperpnoea, abnormal eye movements, ataxia and intellectual disability. JSRD are clinically and genetically heterogeneous, and, to date, a total of 17 causative genes are known. We applied whole-exome sequencing (WES) to five JSRD families and found mutations in all: either CEP290, TMEM67 or INPP5E was mutated. Compared with conventional Sanger sequencing, WES appears to be advantageous with regard to speed and cost, supporting its potential utility in molecular diagnosis.
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Acknowledgements
We thank the patients and their families for their participation in this study. This work was supported by research grants from the Ministry of Health, Labor and Welfare (HS, N Matsumoto, N Miyake), the Japan Science and Technology Agency (N Matsumoto), the Strategic Research Program for Brain Sciences (N Matsumoto) and a Grant-in-Aid for Scientific Research on Innovative Areas-(Transcription cycle)-from the Ministry of Education, Culture, Sports, Science and Technology of Japan (N Matsumoto), a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science (N Matsumoto), a Grant-in-Aid for Young Scientist from Japan Society for the Promotion of Science (HS, N Miyake) and a grant from the Takeda Science Foundation (N Matsumoto, N Miyake).
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The URLs for data presented herein are as follows
Novoalign, http://www.novocraft.com/main/index.php
Burrows-Wheeler Aligner, http://bio-bwa.sourceforge.net/
SIFT, http://sift.jcvi.org/
PolyPhen-2, http://genetics.bwh.harvard.edu/pph2/
Mutation Taster, http://neurocore.charite.de/MutationTaster/
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Tsurusaki, Y., Kobayashi, Y., Hisano, M. et al. The diagnostic utility of exome sequencing in Joubert syndrome and related disorders. J Hum Genet 58, 113–115 (2013). https://doi.org/10.1038/jhg.2012.117
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DOI: https://doi.org/10.1038/jhg.2012.117
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