Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT, USA.
Eur J Hum Genet. 2018 Mar;26(3):293-302. doi: 10.1038/s41431-017-0042-x. Epub 2018 Jan 22.
Chromosome 22q13.3 deletion (Phelan McDermid) syndrome (PMS) is a rare genetic neurodevelopmental disorder resulting from deletions or other genetic variants on distal 22q. Pathological variants of the SHANK3 gene have been identified, but terminal chromosomal deletions including SHANK3 are most common. Terminal deletions disrupt up to 108 protein-coding genes. The impact of these losses is highly variable and includes both significantly impairing neurodevelopmental and somatic manifestations. The current review combines two metrics, prevalence of gene loss and predicted loss pathogenicity, to identify likely contributors to phenotypic expression. These genes are grouped according to function as follows: molecular signaling at glutamate synapses, phenotypes involving neuropsychiatric disorders, involvement in multicellular organization, cerebellar development and functioning, and mitochondrial. The likely most impactful genes are reviewed to provide information for future clinical and translational investigations.
22q13.3 号染色体缺失（Phelan-McDermid）综合征（PMS）是一种罕见的遗传性神经发育障碍，由远端 22q 上的缺失或其他遗传变异引起。已经发现 SHANK3 基因的病理性变异，但包括 SHANK3 在内的末端染色体缺失最为常见。末端缺失会破坏多达 108 个编码蛋白的基因。这些缺失的影响差异很大，既包括严重的神经发育和躯体表现受损。本综述结合了两个指标，即基因缺失的普遍性和预测的致病性缺失，以确定表型表达的可能贡献者。这些基因根据功能分为以下几类：谷氨酸突触的分子信号转导、涉及神经精神疾病的表型、参与细胞间组织、小脑发育和功能以及线粒体。对可能最具影响力的基因进行了综述，为未来的临床和转化研究提供信息。
