Supplementary Material for: Dandy-Walker Malformation in a girl with DDX3X-related intellectual disability

We report on a 4 years old female patient who presented with severe intellectual disability, autistic features, hyperlaxity of joints and progressive scoliosis. Whole exome sequencing identified a novel de novo missense variant (c.976C>T; p.Arg326Cys) in DDX3X. The girl was born with congenital diaphragmatic hernia a finding which had not previously been associated with variants in DDX3X. Her brain MRI showed hypogenesis of corpus callosum, ventriculomegaly, frontal and perisylvian polymicrogyria and hypoplastic pons in addition to Dandy-walker malformation. Our results confirmed the phenotype and genotype correlation of missense variants and the polymicrogyria. Moreover, it further expands the knowledge of the phenotypic and molecular features of DDX3X-related intellectual disability.

本研究报告一例4岁女性患者，该患者表现为重度智力障碍、自闭症特征、关节过度松弛以及进行性脊柱侧凸。全外显子组测序（whole exome sequencing）在DDX3X基因中检测到一种新型从头错义变异（c.976C>T; p.Arg326Cys）。该患儿出生时即患有先天性膈疝，这一表型此前从未有报道与DDX3X基因变异相关联。其脑部磁共振成像（brain MRI）结果显示，除丹迪-沃克畸形（Dandy-Walker malformation）外，还存在胼胝体发育不全、脑室扩大、额区及围外侧裂多小脑回以及脑桥发育不良。本研究结果证实了错义变异与多小脑回的表型-基因型关联。此外，本研究进一步拓展了关于DDX3X相关智力障碍的表型与分子特征的认知。