# CAPRIN1 (Cell Cycle-Associated Protein 1)-Related Neurodevelopmental Disorder: A Novel Mutation With Ataxia

## TL;DR

A new mutation in the CAPRIN1 gene is linked to a neurodevelopmental disorder with symptoms like ataxia, speech delay, and autism.

## Contribution

A novel de novo nonsense mutation in CAPRIN1 is reported, expanding the known genetic basis of this neurodevelopmental disorder.

## Key findings

- The patient had a de novo CAPRIN1 mutation (c.1045 C > T, p.Q349*) associated with neurodevelopmental symptoms.
- The mutation is consistent with loss of function and aligns with previously reported CAPRIN1-related phenotypes.
- Ataxia was a notable feature in this case, adding to the clinical spectrum of CAPRIN1 mutations.

## Abstract

Mutations in the cell cycle-associated protein 1 (CAPRIN1) gene have been shown to present with language impairment, speech delay, intellectual disability, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), respiratory problems, limb and skeletal anomalies, developmental delay, feeding difficulties, seizures, ophthalmologic problems, cerebellar ataxia, dysmorphic features, and hearing loss. CAPRIN1 is involved in regulating the transport and translation of neuronal mRNAs, which encode for cell proliferation and migration proteins, and has been identified as a core component of stress granules. The majority of reported pathogenic mutations in the CAPRIN1 gene result in decreased protein levels and haploinsufficiency; however, they can also result in protein expansion.

We present the case of a patient with ASD, gross motor delay, fine motor delay, speech delay, mixed receptive-expressive language disorder, incontinence, and ADHD. Whole exome sequencing was significant for a likely pathogenic variant in the maternally inherited CAPRIN1 gene, c. 1045 C > T, p. (Q349*), with clinical correlation supporting a diagnosis of CAPRIN1-related neurodevelopmental disorder. Further analysis demonstrated that the patient’s likely pathogenic variant in the CAPRIN1 gene, c. 1045 C > T, p. (Q349*), was a nonsense mutation, de novo and heterozygous, likely resulting in loss of function of the CAPRIN1 protein. This novel mutation in the CAPRIN1 gene has not been previously described in the literature. This novel variant is consistent with the most common identified CAPRIN1 mutations, and his phenotypic presentation included the most common symptoms reported with CAPRIN1 mutations, including language impairment and speech delay, ADHD, ASD, respiratory symptoms, as well as ataxia.