Receptive vocabulary, memory span, and speech articulation in Pakistani children with developmental language disorders.

This study aimed to find the association of receptive vocabulary in the development of speech and language among school-going children (4-13 years) with language disorders. On the basis of non-verbal receptive vocabulary and percentage correct consonants (PCC) scores, children from public schools in Punjab, Pakistan with speech and language issues were separated into three groups; Speech sound disordered (SSD, N = 15), Language Impaired (LI) comorbid with SSD (N = 42) and typically developed (TD, N = 15). Urdu version of Peabody picture vocabulary test, fourth edition (U-PPVT-4), Digit memory test (DMT), and Test for assessment of articulation and phonology in Urdu (TAAPU) were used to assess non-verbal receptive vocabulary, Short-term memory (STM), Working memory (WM), and SSD. Correlation and regression analyses were performed to find the association of receptive vocabulary with other measures used. Receptive vocabulary, STM, WM, omission, substitution, and PCC scores were significantly different (p < 0.01) when compared among LI+SSD, SSD, and TD groups. Regression analysis showed that receptive vocabulary was significantly associated with STM and WM in the LI+SSD group. A positive correlation was found between the U-PPVT-4 standard score with STM and WM for LI+SSD and SSD groups. Our findings in Urdu-speaking children suggested that STM and WM were less developed in children with speech and language impairments. Moreover, children with speech and language deficits not only had weaker receptive vocabulary but also attention should be given to improving STM and WM that contribute to LI.

Working memory span and receptive vocabulary assessment in Urdu speaking children with speech sound disorder.

Emerging evidence suggests that impaired speech may be related to reduced working memory (WM). The current study aimed to validate and compare the influence of articulation, short-term memory (STM), WM, and receptive vocabulary abilities of Pakistani children with speech sound disorder (SSD; N = 50) versus typically developing (TD; N = 30) children aged 7-13 years. Assessments included the Test for Assessment of Articulation and Phonology in Urdu (TAAPU), Peabody Picture Vocabulary Test-4, translated to Urdu (U-PPVT-4), and Digit Memory Test (DMT) used to determine speech articulation, receptive vocabulary, and memory abilities respectively. The percentage correct consonants (PCC) score was used to divide the SSD group further into SSD severity groups. The TD and SSD groups significantly differed in performance on all tasks (p < 0.05). Moreover, the SSD severity groups showed significant differences (p < 0.0001) in performance on different components of TAAPU (total errors and substitution errors) and DMT tasks. However, the SSD severity groups did not show significant differences in performance on the U-PPVT-4. Correlational analyses indicate statistically significant correlations of PCC with STM, WM, and receptive vocabulary. Regression analyses suggested that both WM and STM contribute to speech intelligibility in children with SSD. Our findings in Urdu-speaking children support previous results in English-speaking children suggesting the articulation skills, receptive vocabulary, STM, and WM were less developed in children with SSD than in TD children.

Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment.

Language impairment (LI) is highly heritable and aggregates in families. Genetic investigation of LI has revealed many chromosomal regions and genes of interest, though very few studies have focused on rare variant analysis in non-English speaking or non-European samples. We selected four candidate genes (TM4SF20, NFXL1, CNTNAP2 and ATP2C2) strongly suggested for specific language impairment (SLI), a subtype of LI, and investigated rare protein coding variants through Sanger sequencing of probands with LI ascertained from Pakistan. The probands and their family members completed a speech and language family history questionnaire and a vocabulary measure, the Peabody Picture Vocabulary Test-fourth edition (PPVT-4), translated to Urdu, the national language of Pakistan. Our study aimed to determine the significance of rare variants in these SLI candidate genes through segregation analysis in a novel population with a high rate of consanguinity. In total, we identified 16 rare variants (according to the rare MAF in the global population in gnomAD v2.1.1 database exomes), including eight variants with a MAF <0.5 % in the South Asian population. Most of the identified rare variants aggregated in proband's families, one rare variant (c.*9T>C in CNTNAP2) co-segregated in a small family (PKSLI-64) and another (c.2465C>T in ATP2C2) co-segregated in the proband branch (PKSLI-27). The lack of complete co-segregation of most of the identified rare variants indicates that while these genes could be involved in overall risk for LI, other genes are likely involved in LI in this population. Future investigation of these consanguineous families has the potential to expand our understanding of gene function related to language acquisition and impairment.

A genome-wide analysis in consanguineous families reveals new chromosomal loci in specific language impairment (SLI).

Language is a uniquely human ability, and failure to attain this ability can have a life-long impact on the affected individuals. This is particularly true for individuals with specific language impairment (SLI), which is defined as an impairment in normal language development in the absence of any other developmental disability. Although SLI displays high heritability, family-based linkage studies have been hampered by an unclear mode of Mendelian segregation, variable disease penetrance, and heterogeneity of diagnostic criteria. We performed genome-wide parametric linkage analysis and homozygosity mapping in 14 consanguineous families from Pakistan segregating SLI. Linkage analysis revealed a multipoint LOD score of 4.18 at chromosome 2q in family PKSLI05 under a recessive mode of inheritance. A second linkage score of 3.85 was observed in family PKSLI12 at a non-overlapping locus on chromosome 2q. Two other suggestive linkage loci were found in family PKSLI05 on 14q and 22q with LOD scores of 2.37 and 2.23, respectively, that were also identified in homozygosity mapping. Reduction to homozygosity was observed on chromosomes 2q, 5p, 8q, 14q, 17q, and 22q. Each homozygosity region occurred in multiple PKSLI families. We report new SLI loci on chromosomes 2 and 8 and confirm suggestive SLI linkage loci on chromosomes 5, 14, 17, and 22 reported previously in the population of Robinson Crusoe Island. These findings indicate that linkage and homozygosity mapping in consanguineous families can improve genetic analyses in SLI and suggest the involvement of additional genes in the causation of this disorder.