Abstract

Mutations in the PQBP1 gene are associated with Renpenning syndrome (RENS1, MIM# 309500). Most cases are characterized by intellectual disability, but a detailed neuropsychological profile has not yet been established. The present case study of a 8.5 years-old male child with a missense novel mutation in the PQBP1 gene expands existing understanding of this syndrome by presenting a milder clinical and neuropsychological phenotype. Whole exome trio analysis sequencing revealed a maternally inherited PQBP1 missense mutation in chromosome X [NM_001032383.1, c.727C > T (p.Arg243Trp)]. Variant functional studies demonstrated a significant reduction in the interaction between PQBP1 and the component of the nuclear pre-mRNA splicing machinery, U5-15KD. A comprehensive neuropsychological assessment revealed marked deficits in processing speed, attention and executive functioning (including planning, inhibitory control and working memory) without intellectual disability. Several components of language processing were also impaired. These results support that this mutation partially disrupts the function of this gene, which is known to play critical roles in embryonic and neural development. As most of the genomic PQBP1 abnormalities associated with intellectual disability have been found to be loss-of-function mutations, we hypothesize that a partial loss-of-function of this variant is associated with a mild behavioral and neuropsychological phenotype.

摘要

PQBP1基因的突变与人盆宁综合征（RENS1，MIM# 309500）有关。大多数病例以智力残疾为特征，但尚未建立详细的神经心理学特征。目前对一名 8.5 岁男童的 PQBP1 基因错义新突变的案例研究通过呈现较温和的临床和神经心理学表型扩展了对该综合征的现有理解。全外显子组三重分析测序揭示了染色体 X 中的母系遗传PQBP1错义突变 [NM_001032383.1, c.727C > T (p.Arg243Trp)]。变体功能研究表明PQBP1之间的相互作用显着减少以及核前mRNA剪接机制的组成部分，U5-15KD。一项全面的神经心理学评估显示，在没有智力障碍的情况下，处理速度、注意力和执行功能（包括计划、抑制控制和工作记忆）存在显着缺陷。语言处理的几个组成部分也受损。这些结果支持这种突变部分破坏了该基因的功能，已知该基因在胚胎和神经发育中起关键作用。由于已发现与智力残疾相关的大多数基因组PQBP1异常是功能丧失突变，我们假设该变体的部分功能丧失与轻度行为和神经心理学表型有关。