論文

査読有り 国際誌
2020年5月

A novel PAK1 variant causative of neurodevelopmental disorder with postnatal macrocephaly.

Journal of human genetics
  • Sachiko Ohori
  • ,
  • Satomi Mitsuhashi
  • ,
  • Revital Ben-Haim
  • ,
  • Eli Heyman
  • ,
  • Toru Sengoku
  • ,
  • Kazuhiro Ogata
  • ,
  • Naomichi Matsumoto

65
5
開始ページ
481
終了ページ
485
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s10038-020-0728-8

p21-activated kinases (PAKs) are protein serine/threonine kinases stimulated by Rho-family p21 GTPases such as CDC42 and RAC. PAKs have been implicated in several human disorders, with pathogenic variants in PAK3 associated with intellectual disability and several PAK members, especially PAK1 and PAK4, overexpressed in human cancer. Recently, de novo PAK1 variants were reported to be causative of neurodevelopmental disorder (ND) with secondary macrocephaly in three patients. We herein report a fourth patient with ND, epilepsy, and macrocephaly caused by a de novo PAK1 missense variant. Two previously reported missense PAK1 variants functioned as activating alleles by reducing PAK1 homodimerization. To examine the pathogenicity of the identified novel p.Ser110Thr variant, we carried out in silico structural analysis. Our findings suggest that this variant also prevents PAK1 homodimerization, leading to constitutive PAK1 activation.

リンク情報
DOI
https://doi.org/10.1038/s10038-020-0728-8
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32005903
ID情報
  • DOI : 10.1038/s10038-020-0728-8
  • PubMed ID : 32005903

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