Variants in KIF2A cause broad clinical presentation; the computational structural analysis of a novel variant in a patient with a cortical dysplasia, complex, with other brain malformations 3

被引：6

作者：

Hatano, Maiko ^{[1
]}

Fukushima, Hiroko ^{[1
,2
]}

Ohto, Tatsuyuki ^{[1
,2
]}

Ueno, Yuichi ^{[1
]}

Saeki, Saki ^{[1
]}

Enokizono, Takashi ^{[1
]}

Tanaka, Ryuta ^{[1
]}

Tanaka, Mai ^{[1
]}

Imagawa, Kazuo ^{[1
]}

Kanai, Yu ^{[1
]}

Kato, Mitsuhiro ^{[3
,4
]}

Shiraku, Hiroshi ^{[5
]}

Suzuki, Hisato ^{[6
]}

Uehara, Tomoko ^{[6
]}

Takenouchi, Toshiki ^{[6
]}

Kosaki, Kenjiro ^{[6
]}

Takada, Hidetoshi ^{[1
,2
]}

机构：

[1] Univ Tsukuba Hosp, Dept Pediat, Ibaraki, Japan

[2] Univ Tsukuba, Dept Child Hlth, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan

[3] Showa Univ, Dept Pediat, Sch Med, Tokyo, Japan

[4] Yamagata Univ, Dept Pediat, Fac Med, Yamagata, Japan

[5] JA Toride Med Ctr, Dept Pediat, Ibaraki, Japan

[6] Keio Univ, Ctr Med Genet, Sch Med, Tokyo, Japan

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2021年 / 185卷 / 04期

关键词：

cortical dysplasia; complex; with other brain malformations 3; developmental delay; KIF2A; lissencephaly; neural migration; MUTATIONS;

D O I：

10.1002/ajmg.a.62084

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Cortical dysplasia, complex, with other brain malformations 3 (CDCBM3) is a rare autosomal dominant syndrome caused by Kinesin family Member 2A (KIF2A) gene mutation. Patients with CDCBM3 exhibit posterior dominant agyria/pachygyria with severe motor dysfunction. Here, we report an 8-year-old boy with CDCBM3 showing a typical, but relatively mild, clinical presentation of CDCBM3 features. Whole-exome sequencing identified a heterozygous mutation of NM_001098511.2:c.1298C>A [p.(Ser433Tyr)]. To our knowledge, the mutation has never been reported previously. The variant was located distal to the nucleotide binding domain (NBD), in which previously-reported variants in CDCBM3 patients have been located. The computational structural analysis showed the p.433 forms the pocket with NBD. Variants in KIF2A have been reported in the NBD for CDCBM3, in the kinesin motor 3 domain, but not in the NBD in epilepsy, and outside of the kinesin motor domain in autism spectrum syndrome, respectively. Our patient has a variant, that is not in the NBD but at the pocket with the NBD, resulting in a clinical features of CDCBM3 with mild symptoms. The clinical findings of patients with KIF2A variants appear restricted to the central nervous system and facial anomalies. We can call this spectrum "KIF2A syndrome" with variable severity.

引用

页码：1113 / 1119

页数：7