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Genetic analysis of adult leukoencephalopathy patients using a custom-designed gene panel.

Authors :
Kunii M
Doi H
Ishii Y
Ohba C
Tanaka K
Tada M
Fukai R
Hashiguchi S
Kishida H
Ueda N
Kudo Y
Kugimoto C
Nakano T
Udaka N
Miyatake S
Miyake N
Saitsu H
Ito Y
Takahashi K
Nakamura H
Tomita-Katsumoto A
Takeuchi H
Koyano S
Matsumoto N
Tanaka F
Source :
Clinical genetics [Clin Genet] 2018 Aug; Vol. 94 (2), pp. 232-238. Date of Electronic Publication: 2018 Jun 08.
Publication Year :
2018

Abstract

Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom-designed gene panel. We selected 55 leukoencephalopathy-related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.<br /> (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Details

Language :
English
ISSN :
1399-0004
Volume :
94
Issue :
2
Database :
MEDLINE
Journal :
Clinical genetics
Publication Type :
Academic Journal
Accession number :
29700822
Full Text :
https://doi.org/10.1111/cge.13371