Open AccessA Novel Heterozygous Missense Variant in the CIAO1 Gene in a Family with Alzheimer’s Disease: The Val67Ile Variant Promotes the Interaction of CIAO1 and Amyloid-β Protein Precursor
Author(s) -
Haitian Nan,
Yeon Jeong Kim,
Mai Tsuchiya,
Toko Fukao,
Noriko Hara,
Atsushi Hagihara,
Kenya Nishioka,
Nobutaka Hattori,
Norikazu Hara,
Takeshi Ikeuchi,
Toshihisa Ohtsuka,
Yoshihisa Takiyama
Publication year - 2021
Publication title -
journal of alzheimer's disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.677
H-Index - 139
eISSN - 1875-8908
pISSN - 1387-2877
DOI - 10.3233/jad-210706
Subject(s) - missense mutation , dementia , gene , genetics , heterozygote advantage , disease , amyloid (mycology) , compound heterozygosity , biology , mutation , medicine , allele , pathology
Familial dementia is a rare inherited disease involving progressive impairment of memory, thinking, and behavior. We report a novel heterozygous pathogenic variant (c.199G > A, p.Val67Ile) in the CIAO1 gene that appears to be co-segregated with Alzheimer’s disease in a Japanese family. Biochemical analysis of CIAO1 protein revealed that the variant increases the interaction of CIAO1 with immature amyloid-β protein precursor (AβPP), but not mature or soluble AβPP, indicating plausible CIAO1 involvement in AβPP processing. Our study indicates that a heterozygous variant in the CIAO1 gene may be closely related to autosomal dominant familial dementia.