PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D.

By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy.

Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.

PPP2R5D相关的神经发育障碍（NDD）是一种罕见的常染色体显性疾病，具有发育迟缓和轻度至重度智力障碍。到目前为止，只有不到30个受影响的个体具有PPP2R5D的复发性从头错义变体。近年来，随着20和40岁之间的发病帕金森据报道，利用相同的p只成年个体。在（Glu200Lys）变种PPP2R5D。

通过三重基因组外显子测序，我们现在在一名29岁女性中鉴定了p。（Glu198Lys）变异体，该变异体表现出与PPP2R5D相关的神经发育障碍的典型临床表现，另外还伴有运动能力下降和左旋多巴反应性，早发性帕金森病（来自她20多岁）。 。因此，脑闪烁显像显示出两侧纹状体中多巴胺转运蛋白的明显减少。

我们的研究结果进一步扩大分子和临床谱PPP2R5D -相关NDD，并确认在成年早期帕金森有关联。这对与PPP2R5D相关的NDD的预后以及在受影响的个体中运动下降和帕金森样症状的治疗管理具有重要意义。