Linkage-exome approach to identify responsible variants for hereditary neurological disorders

Yasuyuki Fukumaki (Medical Institute of Bioregulation,Kyushu University)

Shiroh Miura (Department of Medicine,Kurume University School of Medicine)


Massively parallel sequencing of entire exons facilitates identification of responsible variants for rare hereditary disorders. However,limited availability of family members of the relevant disorder still often hampers this powerful approach because of difficulty in filtrating enormous amount of variants revealed by deep sequencing. To overcome this issue,we designed exome analysis assisted by linkage analysis,named “linkage-exome approach”.

To establish this approach,we take a chance to analyze a four-generation pedigree of a clinically new type autosomal dominant disorder,hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities,urinary disturbance and paroxysmal dry cough (Miura et al. J Neurol Sci 2008). Afterward we will apply this approach to other hereditary neurological disorders,family members of which are currently ascertained such as hereditary myoclonic epilepsy and hereditary asymptomatic hyper CKemia.

Final goals of our project are establishment and evaluation of applicability of the linkage-exome approach for hereditary neurological disorders,leading to development of personalized medicine based on personal genome information.