2024-03-28T09:50:08Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02012281
2023-08-03T05:31:20Z
1642838163960:1642838338003
1642838403551:1642838407795
Comprehensive investigation of CASK mutations and other genetic etiologies in 41 patients with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH)
Hayashi, Shin
Uehara, Daniela Tiaki
Tanimoto, Kousuke
Mizuno, Seiji
Chinen, Yasutsugu
Fukumura, Shinobu
Takanashi, Jun-ichi
Osaka, Hitoshi
Okamoto, Nobuhiko
Inazawa, Johji
The CASK gene (Xp11.4) is highly expressed in the mammalian nervous system and plays several roles in neural development and synaptic function. Loss-of-function mutations of CASK are associated with intellectual disability and microcephaly with pontine and cerebellar hypoplasia (MICPCH), especially in females. Here, we present a comprehensive investigation of 41 MICPCH patients, analyzed by mutational search of CASK and screening of candidate genes using an SNP array, targeted resequencing and whole-exome sequencing (WES). In total, we identified causative or candidate genomic aberrations in 37 of the 41 cases (90.2%). CASK aberrations including a rare mosaic mutation in a male patient, were found in 32 cases, and a mutation in ITPR1, another known gene in which mutations are causative for MICPCH, was found in one case. We also found aberrations involving genes other than CASK, such as HDAC2, MARCKS, and possibly HS3ST5, which may be associated with MICPCH. Moreover, the targeted resequencing screening detected heterozygous variants in RELN in two cases, of uncertain pathogenicity, and WES analysis suggested that concurrent mutations of both DYNC1H1 and DCTN1 in one case could lead to MICPCH. Our results not only identified the etiology of MICPCH in nearly all the investigated patients but also suggest that MICPCH is a genetically heterogeneous condition, in which CASK inactivating mutations appear to account for the majority of cases.
論文
http://purl.org/coar/resource_type/c_6501
Public Library of Science
2018-06-14
VoR
http://hdl.handle.net/20.500.12000/45639
1932-6203
PLOS ONE
8
12
eng
https://doi.org/10.1371/journal.pone.0181791
https://doi.org/10.1371/journal.pone.0181791
open access
Creative Commons Attribution License 4.0
https://creativecommons.org/licenses/by/4.0/