Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech.

IF 6.3 1区 医学 Q1 GENETICS & HEREDITY Molecular Autism Pub Date : 2025-02-13 DOI:10.1186/s13229-025-00642-8
Clothilde Ormieres, Marion Lesieur-Sebellin, Karine Siquier-Pernet, Geoffroy Delplancq, Marlene Rio, Mélanie Parisot, Patrick Nitschké, Cristina Rodriguez-Fontenla, Alison Bodineau, Lucie Narcy, Emilie Schlumberger, Vincent Cantagrel, Valérie Malan
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引用次数: 0

Abstract

Background: Developmental language disorder (DLD) refers to children who present with language difficulties that are not due to a known biomedical condition or associated with autism spectrum disorder (ASD) or intellectual disability (ID). The clinical heterogeneity of language disorders, the frequent presence of comorbidities, and the inconsistent terminology used over the years have impeded both research and clinical practice. Identifying sub-groups of children (i.e. DLD cases without childhood apraxia of speech (CAS)) with language difficulties is essential for elucidating the underlying genetic causes of this condition. DLD presents along a spectrum of severity, ranging from mild speech delays to profound disturbances in oral language structure in otherwise typically intelligent children. The prevalence of DLD is ~ 7-8% or 2% if severe forms are considered. This study aims to investigate a homogeneous cohort of DLD patients, excluding cases of ASD, ID or CAS, using multiple genomic approaches to better define the molecular basis of the disorder.

Methods: Fifteen families, including 27 children with severe DLD, were enrolled. The majority of cases (n = 24) were included in multiplex families while three cases were sporadic. This resulted in a cohort of 59 individuals for whom chromosomal microarray analysis and exome or genome sequencing were performed.

Results: We identified copy number variants (CNVs) predisposing to neurodevelopmental disorders with incomplete penetrance and variable expressivity in two families. These CNVs (i.e., 15q13.3 deletion and proximal 16p11.2 duplication) are interpreted as pathogenic. In one sporadic case, a de novo pathogenic variant in the ZNF292 gene, known to be associated with ID, was detected, broadening the spectrum of this syndrome.

Limitations: The strict diagnostic criteria applied by our multidisciplinary team, including speech-language physicians, neuropsychologists, and paediatric neurologists, resulted in a relatively small sample size, which limit the strength of our findings.

Conclusion: These findings highlight a common genetic architecture between DLD, ASD and ID, and underline the need for further investigation into overlapping neurodevelopmental pathways.

Trial registration: ClinicalTrials.gov Identifier: NCT06660108.

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来源期刊
Molecular Autism
Molecular Autism GENETICS & HEREDITY-NEUROSCIENCES
CiteScore
12.10
自引率
1.60%
发文量
44
审稿时长
17 weeks
期刊介绍: Molecular Autism is a peer-reviewed, open access journal that publishes high-quality basic, translational and clinical research that has relevance to the etiology, pathobiology, or treatment of autism and related neurodevelopmental conditions. Research that includes integration across levels is encouraged. Molecular Autism publishes empirical studies, reviews, and brief communications.
期刊最新文献
Deciphering the genetic basis of developmental language disorder in children without intellectual disability, autism or apraxia of speech. Understanding depression in autism: the role of subjective perception and anterior cingulate cortex volume. Age-related changes in brain signal variability in autism spectrum disorder. "What does 'often' even mean?" Revising and validating the Comprehensive Autistic Trait Inventory in partnership with autistic people. Atypical early neural responses to native and non-native language in infants at high likelihood for developing autism.
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