A mild clinical and neuropsychological phenotype of Renpenning syndrome: A new case report with a maternally inherited PQBP1 missense mutation

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.

Keywords:

• Attention and executive functions
• PQBP1 gene
• renpenning syndrome
• working memory

Ethics approval

The study was carried out in accordance with the Declaration of Helsinki of the World Medical Association (2008) and approved by the Local Ethics Committees (Madrid, Spain; Ref. 30062019). Informed consent was obtained from parents, after full explanation of the procedures.

Disclosure statement

No potential competing interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Additional information

Funding

This work was supported by the Spanish Ministerio de Economía y Competitividad, MINECO [grant number PSI2017-84922-R], and Comunidad de Madrid [grant number SI1/PJI/2019–00061].