Discordant phenotype caused by CASK mutation in siblings with NF1

Hiroaki Murakami; Yuichi Kimura; Yumi Enomoto; Yoshinori Tsurusaki; Moe Akahira-Azuma; Yukiko Kuroda; Megumi Tsuji; Tomohide Goto; Kenji Kurosawa

doi:10.1038/s41439-019-0051-0

Discordant phenotype caused by CASK mutation in siblings with NF1

Hum Genome Var. 2019 Apr 26:6:20. doi: 10.1038/s41439-019-0051-0. eCollection 2019.

Authors

Hiroaki Murakami¹, Yuichi Kimura², Yumi Enomoto², Yoshinori Tsurusaki², Moe Akahira-Azuma¹, Yukiko Kuroda¹, Megumi Tsuji³, Tomohide Goto³, Kenji Kurosawa¹

Affiliations

¹ 1Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan.
² 2Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan.
³ 3Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.

Abstract

With the advent of next-generation sequencing (NGS), a blended phenotype has been shown to be caused by multilocus molecular diagnosis. Here, we present siblings of neurofibromatosis type 1 (NF1) with discordant phenotypes. Further genetic investigation revealed that the younger sister had trisomy 8 mosaicism with a low ratio and a known pathogenic mutation in the CASK gene. This is the first report of a blended phenotype caused by NF1, CASK disorder, and trisomy 8 mosaicism.

Keywords: Disease genetics.