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

Maiko Hatano, Hiroko Fukushima, Tatsuyuki Ohto, Yuichi Ueno, Saki Saeki, Takashi Enokizono, Ryuta Tanaka, Mai Tanaka, Kazuo Imagawa, Yu Kanai, Mitsuhiro Kato, Hiroshi Shiraku, Hisato Suzuki, Tomoko Uehara, Toshiki Takenouchi, Kenjiro Kosaki, Hidetoshi Takada

研究成果: Article査読

抄録

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.

本文言語English
ページ(範囲)1113-1119
ページ数7
ジャーナルAmerican Journal of Medical Genetics, Part A
185
4
DOI
出版ステータスPublished - 2021 4

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

フィンガープリント 「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」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル