What question did this study set out to answer?

To explore the genetic basis of childhood apraxia of speech through exome sequencing and gene analysis.

February 16, 2026Case Reports in Genetics0 citationsOpen Access

Three Unrelated Children With Childhood Apraxia of Speech: Exome Sequencing and Functional Gene Analysis Imply a Role of Laminin‐511 in Early Neurodevelopment

CRCaitlin Raaz LBLaurel A Bruce MGMadhavi K. Ganapathiraju

Key Points

To explore the genetic basis of childhood apraxia of speech through exome sequencing and gene analysis.
Analyzed DNA from three unrelated children with childhood apraxia of speech and their parents via exome sequencing.
Conducted variant filtering on identified genetic variants of interest.
Investigated gene expression rates in the developing cerebellum and protein–protein interactions among key genes.
Identified variants in genes including LRRK2, contributing to genetic heterogeneity in childhood apraxia of speech.
High expression levels of LAMA5 and LAMB1 in the developing cerebellum were observed.
Established a connectome with 32 nodes and 73 edges, suggesting significant interactions among genes of interest.

Abstract

Childhood apraxia of speech (CAS) is characterized by motor discoordination in the speech domain and also in fine and gross motor systems, implicating the early developing cerebellum. Comorbidity with autism spectrum disorder (ASD) and other neurodevelopmental conditions has been observed. The genetic etiology is highly heterogeneous. Here, we present three unrelated individuals with CAS and concomitant fine and gross motor involvement but different genetic variants of interest. The DNA of the cases and their parents underwent exome sequencing and variant filtering. Using publicly available data, the genes of interest derived from the variants were investigated for expression rates in the early developing brain. Known and putative protein–protein interactions among the genes of highest confidence were identified. Of 28 variants in 28 different genes, variants with highest confidence were situated in FOXN4 , LAMA5 , LAMB1 , LRRK2 , and USP17L2 . High gene expression rates in the developing cerebellum were observed for LAMA5 and LAMB1 . These genes encode the α5 and β1 subunits, respectively, of the heterotrimeric extracellular laminin‐511 complex, a major component of the basal membrane in many tissues. Network analysis of the five high‐confidence genes required expansion with only one additional gene, CDK6 , to arrive at a fully connected network. The addition of four genes and inclusion of transcriptional regulation as an additional edge type allowed connecting all 28 genes of interest to arrive at a dense connectome with 32 nodes and 73 edges, representing a network enrichment with p value of < 0.001, suggesting that our network has significantly more interactions than expected under random conditions. We conclude that high levels of genetic heterogeneity converge on a functional gene network governed by stimulation of cells through laminin‐511 with shared direct or regulatory expression in the developing cerebellum and phenotypic overlaps of CAS, ASD, and other neurodevelopmental disorders.

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