Primary microcephaly (PM) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci identified to date. We report a consanguineous family with PM, intellectual disability and short stature. Using whole exome sequencing, we identified a homozygous frameshift variant in programmed cell death 6 interacting protein (PDCD6IP , c.154_158dup; p.Val54Profs*18). This gene, PDCD6IP , plays an important role in the endosomal sorting complexes required for transport (ESCRT) pathway in the abscission stage of cytokinesis and apoptosis, and is required for normal brain development in mice. The clinical features observed in our patient were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. This study provides evidence that clinical manifestations of PDCD6IP mutations as seen in our patients with PM and ID may be a novel cause for neurodevelopmental disorders.

中文翻译：

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PDCD6IP 编码 ESCRT 复合体的调节因子，在小头畸形中发生突变。

原发性小头畸形 (PM) 是一种高度异质的神经发育障碍，迄今为止已发现许多危险基因和位点。我们报告了一个患有 PM、智力残疾和身材矮小的近亲家庭。使用全外显子组测序，我们在程序性细胞死亡 6 相互作用蛋白 ( PDCD6IP , c.154_158dup; p.Val54Profs*18) 中鉴定出纯合移码变体。该基因PDCD6IP在胞质分裂和细胞凋亡的脱落阶段在转运所需的内体分选复合物 (ESCRT) 途径中起重要作用，并且是小鼠正常大脑发育所必需的。在我们的患者中观察到的临床特征与在PDCD6IP的小鼠和斑马鱼模型中观察到的表型相似先前研究中的突变。这项研究提供的证据表明，在我们的 PM 和 ID 患者中看到的PDCD6IP突变的临床表现可能是神经发育障碍的新原因。