Moresco Giada, Costanza Jole, Santaniello Carlo, Rondinone Ornella, Grilli Federico, Prada Elisabetta, Orcesi Simona, Coro Ilaria, Pichiecchio Anna, Marchisio Paola, Miozzo Monica, Fontana Laura, Milani Donatella
Research Laboratories Coordination Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Ital J Pediatr. 2021 Mar 31;47(1):81. doi: 10.1186/s13052-021-01033-4.
De novo pathogenic variants in the DDX3X gene are reported to account for 1-3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs.
We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.625C > G) by whole exome sequencing (WES). The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome.
This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.
据报道，DDX3X基因的新生致病性变异占女性不明原因智力残疾（ID）的1%-3%，导致一种名为DDX3X综合征（MRXSSB，OMIM #300958）的罕见疾病。除了智力残疾外，这些患者还表现出多种临床表现，包括神经和行为缺陷以及脑部MRI异常。
我们报告了一名10岁女孩，患有精神运动发育迟缓、髓鞘形成延迟和多小脑回（PMG）。我们通过全外显子组测序（WES）在DDX3X基因中鉴定出一个新的新生错义突变（c.625C＞G）。DDX3X基因编码一种依赖ATP的DEAD盒RNA解旋酶，广泛参与通过调节mRNA代谢来调控基因表达。所鉴定的突变位于解旋酶结构域上游，提示可能损害蛋白质活性，从而导致DDX3X依赖的mRNA翻译改变。先证者表现出与该综合征相关的典型PMG表型，但未出现错义DDX3X突变患者中常见的、与更严重临床表现相关的其他临床体征。此外，她有短头畸形，这在女性DDX3X患者中从未有过描述，还有巨舌症，这也从未与该综合征相关联。
该病例扩展了对DDX3X致病性变异及相关DDX3X综合征表型谱的认识。
