Biallelic mutations in the AP4B1 gene, encoding adaptor-related protein complex 4 beta-1 subunit, have been recognized as an important cause of a group of conditions leading to adaptor-related protein complex 4 (AP4)-associated hereditary spastic paraplegia (SPG47). We describe a homozygous, known variant c.1160_1161delCA (p.Thr387fs) that was found in the largest ever group of patients coming from four families. The patients exhibited early hypotonia progressing to spastic paraplegia, microcephaly, epilepsy, and central nervous system (CNS) defects and global developmental delay that are consistent with the nature of SPG47. Our findings expand phenotypic spectrum of SPG47 to include polymorphic seizures, mild/moderate intellectual disability, and intracerebral cysts as well as point to founder mutation in AP4 deficiency disorders in apparently non-consanguineous Polish families without shared ancestry.

中文翻译：

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AP4B1相关的遗传性痉挛性截瘫：与纯合p.Thr387fs变体有关的表型谱的扩展

AP4B1中的双等位基因突变编码适配器相关蛋白复合物4β-1亚基的基因被认为是导致导致与适配器相关蛋白复合物4（AP4）相关的遗传性痉挛性截瘫（SPG47）的一组疾病的重要原因。我们描述了一个纯合的已知变体c.1160_1161delCA（p.Thr387fs），该变体存在于来自四个家庭的最大患者群体中。患者表现出早期肌张力低下，进展为痉挛性截瘫，小头畸形，癫痫和中枢神经系统（CNS）缺陷以及整体发育延迟，这与SPG47的性质一致。我们的发现将SPG47的表型范围扩大到包括多态性癫痫发作，轻度/中度智力障碍，