先天性眼外肌纤维化1型（CFEOM1）中驱动蛋白KIF21A的杂合突变。

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

作者信息

Yamada Koki, Andrews Caroline, Chan Wai-Man, McKeown Craig A, Magli Adriano, de Berardinis Teresa, Loewenstein Anat, Lazar Moshe, O'Keefe Michael, Letson Robert, London Arnold, Ruttum Mark, Matsumoto Naomichi, Saito Nakamichi, Morris Lisa, Del Monte Monte, Johnson Roger H, Uyama Eiichiro, Houtman Willem A, de Vries Berendina, Carlow Thomas J, Hart Blaine L, Krawiecki Nicolas, Shoffner John, Vogel Marlene C, Katowitz James, Goldstein Scott M, Levin Alex V, Sener Emin C, Ozturk Banu T, Akarsu A Nurten, Brodsky Michael C, Hanisch Frank, Cruse Robert P, Zubcov Alina A, Robb Richard M, Roggenkäemper Peter, Gottlob Irene, Kowal Lionel, Battu Ravi, Traboulsi Elias I, Franceschini Piergiorgio, Newlin Anna, Demer Joseph L, Engle Elizabeth C

机构信息

Department of Medicine (Genetics), Enders 5, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.

出版信息

Nat Genet. 2003 Dec;35(4):318-21. doi: 10.1038/ng1261. Epub 2003 Nov 2.

DOI:10.1038/ng1261

PMID:14595441

Abstract

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

摘要

先天性眼外肌纤维化1型（CFEOM1；OMIM #135700）是一种常染色体显性斜视疾病，与动眼神经缺陷相关。我们发现，患有CFEOM1的个体在由KIF21A编码的驱动蛋白运动蛋白中存在杂合错义突变。我们在45名先证者中的44名中鉴定出六种不同的突变。主要突变热点位于柄结构域，这突出了KIF21A及其柄在动眼轴形成中的重要新作用。