A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures.

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 with 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 non-word 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.

Similarities and differences in psycho-educational assessments of adolescents with specific language impairments and specific learning disabilities: A challenging differential diagnosis.

Specific Language Impairment (SLI) and Specific Learning Disabilities (SLD) have been the subject of extensive research especially with respect to the connection between them. However, the manifestation of these disorders in adolescence has not been thoroughly investigated. The objective of the present study was to compare the intelligence scores and the reading, oral and written language skills of Greek adolescents with SLI and Greek adolescents with SLD, as assessed during their psycho-educational evaluation, in order to clear the path for diagnosis and intervention. 124 Greek adolescents diagnosed with Specific Learning Disabilities and 76 Greek adolescents diagnosed with Specific Language Impairment aged from 11 to 16 years took part in the study. All participants were assessed in reading, oral language and written language skills and took part in IQ testing. Independent samples t-test, chi-square test, odds ratios and their 95 percent confidence intervals were implemented to determine statistically significant differences. Analyses revealed differences in IQ scores and some differences in the skills assessed, thus indicating that SLI adolescents exhibited more difficulties across most of the basic academic skills, whereas SLD adolescents' difficulties confined to the affected written language skills. Specifically, the observed difference was statistically significant for the total and verbal IQ score, and WISC-III scores also disclosed a significant difference for the similarities and information defisub- tests. Regarding reading skills, SLI adolescents were 4.9 times more likely to exhibit line skipping, 5.8 times more likely to exhibit hesitations, 3.2 times more likely to exhibit repetitions of syllables/words/ phrases, and 8.5 times more likely to exhibit non-acknowledgement of punctuation. Regarding reading comprehension, adolescents with SLI were more likely to have difficulty in retrieving simple information questions, making inferences, and giving titles. Adolescents with SLI were also more likely to have difficulties in story reproduction, giving synonyms/opposites, oral sentence reproduction and auditory oral word reproduction. In the area of written language skills, SLI adolescents were more likely to have poor handwriting, poor content, poor structure, and poor use of punctuation. In adolescence, Specific Language Impairment can be a different manifestation of an ongoing language disorder, which finally appears as a different type of Specific Learning Disability, but with a more generalized nature of learning difficulties. This finding should be interpreted in terms of the importance of differential diagnosis, especially during the challenging period of adolescence.

Specific Language Impairment and Reading Disability: Categorical Distinction or Continuum?

Specific language impairment (SLI) and reading disability (RD) are familial, moderately heritable comorbid developmental disorders. The key deficit of SLI is oral language, whereas children with RD exhibit impairment in learning to read. The present study examines the possible co-occurrence of RD and SLI and the nature of this co-occurrence at a linguistic and a cognitive level in an orthographically consistent language. Four groups of children participated in the study: an RD group ( n = 10), an SLI group ( n = 13), a possible comorbid group ( n = 9), and a control-no deficit group ( n = 20). Analysis showed that all three clinical groups in our sample performed similarly in phonological awareness and naming-speed tasks. However, significant group differences were observed in orthographic processing, reading, semantics, and phonological memory measures, thus supporting the view that SLI and RD are distinct disorders. Results are in line with previous findings indicating that SLI and RD share common characteristics, although the two conditions are manifested with different symptoms.