Chromosome 22q13.3 deletion (Phelan-McDermid) syndrome (PMS, OMIM 606232) is a rare genetic condition that impacts neurodevelopment. PMS most commonly results from heterozygous contiguous gene deletions that include the SHANK3 gene or likely pathogenic variants of SHANK3 (PMS-SHANK3 related). Rarely, chromosomal rearrangements that spare SHANK3 share the same general phenotype (PMS-SHANK3 unrelated). Very recent human and model system studies of genes that likely contribute to the PMS phenotype point to overlap in gene functions associated with neurodevelopment, synaptic formation, stress/inflammation and regulation of gene expression. In this review of recent findings, we describe the functional overlaps between SHANK3 and six partner genes of 22q13.3 (PLXNB2, BRD1, CELSR1, PHF21B, SULT4A1, and TCF20), which suggest a model that explains the commonality between PMS-SHANK3 related and PMS-SHANK3 unrelated classes of PMS. These genes are likely not the only contributors to neurodevelopmental impairments in the region, but they are the best documented to date. The review provides evidence for the overlapping and likely synergistic contributions of these genes to the PMS phenotype.

中文翻译：

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SHANK3 与 Phelan-McDermid 综合征其他基因之间共同病理机制的证据

染色体 22q13.3 缺失 (Phelan-McDermid) 综合征 (PMS, OMIM 606232) 是一种影响神经发育的罕见遗传病。 PMS 最常见的原因是杂合的连续基因缺失，其中包括SHANK3基因或SHANK3的可能致病变异（PMS- SHANK3相关）。罕见的是，不影响SHANK3的染色体重排具有相同的一般表型（PMS- SHANK3无关）。最近对可能导致经前综合症表型的基因进行的人类和模型系统研究表明，与神经发育、突触形成、应激/炎症和基因表达调节相关的基因功能存在重叠。在对最近发现的这篇综述中，我们描述了SHANK3和 22q13.3 的六个伙伴基因（PLXNB2、BRD1、CELSR1、PHF21B、SULT4A1和TCF20 ）之间的功能重叠，这提出了一个模型来解释 PMS- SHANK3相关之间的共性和 PMS- SHANK3不相关的 PMS 类别。这些基因可能不是该地区神经发育障碍的唯一促成因素，但它们是迄今为止最有据可查的。该综述为这些基因对经前综合症表型的重叠和可能的协同贡献提供了证据。