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Purpose: Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method: We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results: A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions: These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI.

Specific language impairment (SLI) is a developmental disorder with substantial genetic contributions. A genome-wide linkage analysis and homozygosity mapping were performed in five consanguineous families from Pakistan. The highest LOD scores of 2.49 at 12p11.22-q11.21 in family PKSLI-31 and 1.92 at 6p in family PKSLI-20 were observed. Homozygosity mapping showed a loss of heterozygosity on 1q25.3-q32.2 and 2q36.3-q37.3 in PKSLI-20. A loss of heterozygosity mapped, in PKSLI-31 and PKSLI-34 flanks, NFXL1 and CNTNAP2, which are genes previously identified in SLI. Our findings report novel SLI loci and corroborate previously reported SLI loci, indicating the utility of a family-based approach. [ABSTRACT FROM AUTHOR]

Speech is the most common means of communication in humans. Any defect in accurate speech production ability results in the development of speech sound disorder (SSD), a condition that can significantly impair an individual's academic performance, social interactions, and relationships with peers and adults. This study investigated the genetic basis of SSD in three Pakistani families. We performed family-based genome-wide parametric linkage analysis and homozygosity mapping in three consanguineous families with SSD from the Punjab province of Pakistan. The Test for Assessment of Articulation and Phonology in Urdu (TAAPU) was used to analyze the speech articulation data and determine the Percentage Correct Consonants (PCC) score. The PCC score defined the affected and unaffected individuals in each family. Parametric linkage analysis revealed a linkage to chromosome 5 (5q21.3-5q23.1) with a significant logarithm of the odds (LOD) score of 3.13 in a Pakistani family with specific language impairment-97 (PKSLI-97) under an autosomal recessive mode of inheritance. The other two families showed a suggestive linkage at 6p22.1, 14q12, and 16q12.1 under the recessive mode of inheritance. Interestingly, homozygosity mapping showed a loss of heterozygosity in the linkage region at 5q15-5q23.1, shared among seven affected (mostly in the younger generation) and one unaffected individual of PKSLI-97. Our analysis identified the 6p22 locus previously implicated in dyslexia, childhood apraxia of speech (CAS), and language impairment, confirming the role of KIAA0319 and DCDC2 in this locus. These findings provide statistical evidence for the genomic regions associated with articulation disorder and offer future opportunities to further the role of genes in speech production. [ABSTRACT FROM AUTHOR]

Purpose: Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method: We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results: A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions: These results are the first to report genomewide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material: https://doi.org/10.23641/asha. 13203218, Most children acquire language without any formal instruction. Contrary to common expectations, language does not come easily to all children. Specific language impairment (SLI) is a language disorder that delays [...]

Individuals with specific language impairment (SLI) struggle with language acquisition despite average non-verbal intelligence and otherwise typical development. One SLI account focuses on grammar acquisition delay. The current study aimed to detect novel rare genetic variants associated with performance on a grammar assessment, the Test of Early Grammatical Impairment (TEGI), in English-speaking children. The TEGI was selected due to its sensitivity and specificity, consistently high heritability estimates, and its absence from all but one molecular genetic study. We performed whole exome sequencing (WES) in eight families with SLI (n = 74 total) and follow-up Sanger sequencing in additional unrelated probands (n = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance (n = 34) from at least two families under two filtering workflows: (1) novel and (2) previously reported candidate genes. Candidate variants were observed on six new genes (PDHA2, PCDHB3, FURIN, NOL6, IQGAP3, and BAHCC1), and two genes previously reported for overall language ability (GLI3 and FLNB). We specifically suggest PCDHB3, a protocadherin gene, and NOL6 are critical for ribosome synthesis, as they are important targets of SLI investigation. The proposed SLI candidate genes associated with TEGI performance emphasize the utility of precise phenotyping and family-based genetic study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies. This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution. We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24. ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity's effect on the Pakistani population. Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants. [ABSTRACT FROM AUTHOR]

Needle Stick Injury (NSI) is a percutaneous piercing wound typically dealing with sharps. Needle stick injuries are the most common health care workers issue worldwide. The causes include various factors like type and design of needle, recapping activity, handling/ transferring specimens, collision between HCWs or sharps, during clean-up, manipulating needles in patient line related work, passing/handling devices or failure to dispose of the needle in puncture proof containers. NSIs may transmit other bacterial, fungal, or viral infections, including blastomycosis, cryptococcosis, diphtheria, herpes, malaria, mycobacteriosis, spotted fever and syphilis. Objectives: To determine frequency of needle stick injury among health care workers. Study Design: Cross-sectional study. Setting: District Headquarter Hospital Layyah. Period: Jan to March 2019. Material & Methods: Sample size was 161. A structured pre-tested questionnaire containing both open and close-ended questions was administered during the period of Jan-March 2019. Results: Out of 161 participants, 114 (70.8%) reported having a needle stick injury at least once during their clinical practice and the frequency of NSIs was significantly higher among nurses (76.7%) as compared to Doctors (50%), Laboratory staff (45.5%) and waste handlers (70.8 %). Conclusion: Study concludes that in absence of the routine collection of accurate data on NSIs, small studies have been useful in highlighting which groups of HCWs are most at risk from NSIs. [ABSTRACT FROM AUTHOR]

Specific language impairment (SLI) is a common neurodevelopmental disorder (NDD) that displays high heritability estimates. Genetic studies have identified several loci, but the molecular basis of SLI remains unclear. With the aim to better understand the genetic architecture of SLI, we performed whole-exome sequencing (WES) in a single family (ID: 489; n = 11). We identified co-segregating rare variants in three new genes: BUD13, APLP2, and NDRG2. To determine the significance of these genes in SLI, we Sanger sequenced all coding regions of each gene in unrelated individuals with SLI (n = 175). We observed 13 additional rare variants in 18 unrelated individuals. Variants in BUD13 reached genome-wide significance (p-value < 0.01) upon comparison with similar variants in the 1000 Genomes Project, providing gene level evidence that BUD13 is involved in SLI. Additionally, five BUD13 variants showed cohesive variant level evidence of likely pathogenicity. Bud13 is a component of the retention and splicing (RES) complex. Additional supportive evidence from studies of an animal model (loss-of-function mutations in BUD13 caused a profound neural phenotype) and individuals with an NDD phenotype (carrying a CNV spanning BUD13), indicates BUD13 could be a target for investigation of the neural basis of language. [ABSTRACT FROM AUTHOR]