Expanding the Molecular Landscape of Childhood Apraxia of Speech: Evidence from a Single-center Experience

Overview

Journal Front Neurosci

Date 2024 Oct 9

PMID 39381681

Authors

Daniela Formicola

Irina Podda

Elia Dirupo

Elena Andreucci

Sabrina Giglio

Paola Cipriani

Clara Bombonato

Filippo Maria Santorelli

Anna Chilosi

Affiliations

Soon will be listed here.

Abstract

Background: Childhood apraxia of speech (CAS) is a genetically heterogeneous pediatric motor speech disorder. The advent of whole exome sequencing (WES) and whole genome sequencing techniques has led to increased identification of pathogenic variants in CAS genes. In an as yet uncharacterized Italian cohort, we aimed both to identify new pathogenic gene variants associated with CAS, and to confirm the disease-related role of genes already reported by others. We also set out to refine the clinical and neurodevelopmental characterization of affected children, with the aim of identifying specific, gene-related phenotypes.

Methods: In a single-center study aiming to explore the genetic etiology of CAS in a cohort of 69 Italian children, WES was performed in the families of the 34 children found to have no copy number variants. Each of these families had only one child affected by CAS.

Results: High-confidence (HC) gene variants were identified in 7/34 probands, in two of whom they affected and , thus confirming the involvement of these genes in speech impairment. The other probands carried variants in low-confidence (LC) genes, and 20 of these variants occurred in genes not previously reported as associated with CAS. , and genes were found to be more enriched in the CAS cohort compared to control individuals. Our results also showed that most HC genes are involved in epigenetic mechanisms and are expressed in brain regions linked to language acquisition processes.

Conclusion: Our findings confirm a relatively high diagnostic yield in Italian patients.

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