Buchumschlag

De novo variants in CELF2 that disrupt the nuclear localization signal cause developmental and epileptic encephalopathy

We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has m...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Itai, Toshiyuki (VerfasserIn) , Hamanaka, Kohei (VerfasserIn) , Sasaki, Kazunori (VerfasserIn) , Wagner, Matias (VerfasserIn) , Kotzaeridou, Urania (VerfasserIn) , Brösse, Ines (VerfasserIn) , Ries, Markus (VerfasserIn) , Kobayashi, Yu (VerfasserIn) , Tohyama, Jun (VerfasserIn) , Kato, Mitsuhiro (VerfasserIn) , Ong, Winnie P. (VerfasserIn) , Chew, Hui B. (VerfasserIn) , Rethanavelu, Kavitha (VerfasserIn) , Ranza, Emmanuelle (VerfasserIn) , Blanc, Xavier (VerfasserIn) , Uchiyama, Yuri (VerfasserIn) , Tsuchida, Naomi (VerfasserIn) , Fujita, Atsushi (VerfasserIn) , Azuma, Yoshiteru (VerfasserIn) , Koshimizu, Eriko (VerfasserIn) , Mizuguchi, Takeshi (VerfasserIn) , Takata, Atsushi (VerfasserIn) , Miyake, Noriko (VerfasserIn) , Takahashi, Hidehisa (VerfasserIn) , Miyagi, Etsuko (VerfasserIn) , Tsurusaki, Yoshinori (VerfasserIn) , Doi, Hiroshi (VerfasserIn) , Taguri, Masataka (VerfasserIn) , Antonarakis, Stylianos E. (VerfasserIn) , Nakashima, Mitsuko (VerfasserIn) , Saitsu, Hirotomo (VerfasserIn) , Miyatake, Satoko (VerfasserIn) , Matsumoto, Naomichi (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2021
In: Human mutation
Year: 2020, Jahrgang: 42, Heft: 1, Pages: 66-76
ISSN:1098-1004
DOI:https://doi.org/10.1002/humu.24130
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/humu.24130
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.24130
Volltext
Verfasserangaben:Toshiyuki Itai, Kohei Hamanaka, Kazunori Sasaki, Matias Wagner, Urania Kotzaeridou, Ines Brösse, Markus Ries, Yu Kobayashi, Jun Tohyama, Mitsuhiro Kato, Winnie P. Ong, Hui B. Chew, Kavitha Rethanavelu, Emmanuelle Ranza, Xavier Blanc, Yuri Uchiyama, Naomi Tsuchida, Atsushi Fujita, Yoshiteru Azuma, Eriko Koshimizu, Takeshi Mizuguchi, Atsushi Takata, Noriko Miyake, Hidehisa Takahashi, Etsuko Miyagi, Yoshinori Tsurusaki, Hiroshi Doi, Masataka Taguri, Stylianos E. Antonarakis, Mitsuko Nakashima, Hirotomo Saitsu, Satoko Miyatake, Naomichi Matsumoto
Beschreibung
Zusammenfassung:We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.
Beschreibung:First published: 01 November 2020
Gesehen am 25.05.2021
Beschreibung:Online Resource
ISSN:1098-1004
DOI:https://doi.org/10.1002/humu.24130

Ähnliche Einträge