Enrichment of rare copy number variation in children with developmental language disorder

Kalnak, Nelli; Stamouli, Sofia; Peyrard-Janvid, Myriam; Rabkina, Ielyzaveta; Becker, Martin; Klingberg, Torkel; Kere, Juha; Forssberg, Hans; Tammimies, Kristiina

doi:10.1111/cge.13389

Cited by 22 publications

(42 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other detected deletions were identified in 18p11.32-p11.22 and Xp22.31-p22.33 loci. Although the proportion is low, it should be noted that this locus overlaps with other neurodevelopmental disorders [131] . Several other minor reports exist, such as a balanced t(10;15) translocation in a male patient with developmental language disorder [132] .…”

Section: C-maf Inducing Protein and Atpase Secretory Pathway Ca 2+ Trmentioning

confidence: 90%

Genomics of Speech and Language Disorders

Guerra¹,

Cacabelos²

2018

Preprint

View full text Add to dashboard Cite

There are multiple factors involved in speech and language. Investigating animal models, mainly through songbirds, have allowed a better understanding of the language process. Verbal dyspraxia, dysarthria, speech sound disorder, and stuttering are some examples of speech disorders, and specific language disorder, aphasia and, dyslexia of language disorders. More complex syndromes such as Autism-spectrum disorders, Down’s or Fragile X have more variable features. Genetic factors, such as hereditary or de novo mutations may be responsible for their development. In addition, most of them are involved in neurodevelopment with a huge range of molecular mechanisms and pathways that interact with each other, and there may be co-morbidity with other communication disorders or develop phenotypes unrelated to communication. Genes with heterogeneous functions in speech and language such as FOXP1, FOXP2, KIAA0319, ROBO1, APOE or CNTNAP2 are some examples. Epigenetic factors, especially miRNAs, influence their expressiveness. The genomics of these disorders allows us to understand language acquisition, carry out early detection strategies, genetic counseling and optimize future treatments, not only in communication disorders but also those neurological alterations that incorporate these mutations.

show abstract

Section: C-maf Inducing Protein and Atpase Secretory Pathway Ca 2+ Trmentioning

confidence: 90%

Genomics of Speech and Language Disorders

Guerra¹,

Cacabelos²

2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In the present cross-sectional study, we aim to explore the reading decoding skills of a population of 61 Swedish-speaking children with DLD, aged 8-12 years, attending school years 1-5 in language units for children with severe DLD. The research questions are: [27,42,43]. Children are usually referred to these schools at the age of six by clinical speech-language pathologists or psychologists due to pervasive and persistent DLD.…”

Section: Aimsmentioning

confidence: 99%

Description and prediction of reading decoding skills in Swedish children with Developmental Language Disorder

Kalnak

Sahlén

2020

Logopedics Phoniatrics Vocology

View full text Add to dashboard Cite

Aim: Research is lacking in terms of reading decoding skills among clinical samples of Swedish-speaking children with Developmental Language Disorder (DLD). Method: The present cross-sectional study included a sample of 61 children (8-12 years) with DLD attending school language units, years 1 to 5. Our purpose was to study reading decoding skills and predictors for decoding, such as a phonological processing skill (nonword repetition), working memory, and a family history of literacy problems. Results: The results on a combined measure of the word and nonword decoding indicated that only 18% of the children had age-adequate decoding skills. The proportion of age-adequate decoders did not change noticeably with the school year. The participants' decoding skills showed larger deviations to test norm means with higher school years. Hierarchical regression analysis showed that the best predictors of decoding skills were measures of working memory and nonword repetition, followed by school year. These factors significantly contributed to the variance in decoding among our sample of children with DLD. A family history of literacy problems made no contribution to the variance. Conclusions: The findings emphasize the necessity of assessing and following up on literacy development in children with DLD.

show abstract

“…Chromosomal rearrangements and copy number variants (CNV) have also been implicated in the aetiology of language impairment. Children with SLI show a higher frequency of sex chromosome aneuploidies (38), and an increased CNV burden compared to population controls (39,40). A balanced translocation interrupting the gene SEMA6D (41) has been identified in a child with SLI.…”

Section: Introductionmentioning

confidence: 99%

A rare missense variant in theATP2C2gene is associated with language impairment and related measures

Martinelli

Rice

Talcott

et al. 2021

Preprint

View full text Add to dashboard Cite

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N=360) compared to cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24,046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N=42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N=1825) (minimum p = 0.002 for nonword reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.

show abstract

Enrichment of rare copy number variation in children with developmental language disorder

Cited by 22 publications

References 50 publications

Genomics of Speech and Language Disorders

Genomics of Speech and Language Disorders

Description and prediction of reading decoding skills in Swedish children with Developmental Language Disorder

A rare missense variant in theATP2C2gene is associated with language impairment and related measures

Contact Info

Product

Resources

About