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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.

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 [...]

Genetic factors are important contributors to language and learning disorders, and discovery of the underlying genes can help delineate the basic neurological pathways that are involved. This information, in turn, can help define disorders and their perceptual and processing deficits. Initial molecular genetic studies of dyslexia, for example, appear to converge on defects in neuronal and axonal migration. Further study of individuals with abnormalities of these genes may lead to the recognition of characteristic cognitive deficits attributable to the neurological dysfunction. Such abnormalities may affect other disorders as well, and studies of co-morbidity of dyslexia with attention deficit disorder and speech sound disorder are helping to define the scope of these genes and show the etiological and cognitive commonalities between these conditions. The genetic contributions to specific language impairment (SLI) are not as well defined at this time, but similar molecular approaches are being applied to identify genes that influence SLI and comorbid disorders. While there is co-morbidity of SLI with dyslexia, it appears that most of the common genetic effects may be with the language characteristics of autism spectrum disorders rather than with dyslexia and related disorders. Identification of these genes and their neurological and cognitive effects should lay out a functional network of interacting genes and pathways that subserve language development. Understanding these processes can form the basis for refined procedures for diagnosis and treatment. (Contains 2 tables.)

Background: Speech sound disorder (SSD) is a common childhood disorder characterized by developmentally inappropriate errors in speech production that greatly reduce intelligibility. SSD has been found to be associated with later reading disability (RD), and there is also evidence for both a cognitive and etiological overlap between the two disorders. The present study tested whether SSD is linked to replicated risk loci for RD. Method: One hundred and eleven probands with SSD and their 76 siblings were tested with measures of speech, phonological memory (Nonword Repetition--NWR), and phonological awareness and genotyped for linkage markers on chromosomes 1p36, 6p22, and 15q21. Both single point and multipoint linkage were tested with multiple methods. Results: The speech and NWR phenotypes were linked to the RD loci on chromosomes 6 and 15, with suggestive results for the RD locus on chromosome 1. Conclusions: It now appears that several RD loci are pleiotropic for SSD, extending the findings of Stein et al. (2004) for the RD locus on Chromosome 3.

This study investigated the role of the myelin oligodendrocye glycoportein (MOG) gene to reading disability in 22 children with dyslexia and 96 random controls. Results suggest that, although alleles in the MOG gene may be in linkage disequilibrium with a locus that contributes to reading disability, the MOG gene itself is probably not involved. (Contains references.) (Author/DB)

This article examines Gene x Environment (G x E) interactions in two comorbid developmental disorders--reading disability (RD) and attention-deficit/hyperactivity disorder (ADHD)--as a window on broader issues on G x E interactions in developmental psychology. The authors first briefly review types of G x E interactions, methods for detecting them, and challenges researchers confront in interpreting such interactions. They then review previous evidence for G x E interactions in RD and ADHD, the directions of which are opposite to each other: bioecological for RD and diathesis stress for ADHD. Given these results, the authors formulate and test predictions about G x E interactions that would be expected at the favorable end of each symptom dimension (e.g., above-average reading or attention). Consistent with their prediction, the authors found initial evidence for a resilience interaction for above-average reading: higher heritability in the presence of lower parental education. However, they did not find a G x E interaction at the favorable end of the ADHD symptom dimension. The authors conclude with implications for future research. Keywords: Gene x Environment interactions, reading disability, attention-deficit/hyperactivity disorder, bioecological interactions, diathesis-stress interactions

DYX2 on 6p22 is the most replicated reading disability (RD) locus. By saturating a previously identified peak of association with single nucleotide polymorphism markers, we identified a large polymorphic deletion that encodes tandem repeats of putative brain-related transcription factor binding sites in intron 2 of DCDC2. Alleles of this compound repeat are in significant disequilibrium with multiple reading traits. RT-PCR data show that DCDC2 localizes to the regions of the brain where fluent reading occurs, and RNA interference studies show that down-regulation alters neuronal migration. The statistical and functional studies are complementary and are consistent with the latest clinical imaging data for RD. Thus, we propose that DCDC2 is a candidate gene for RD. dyslexia | DYX2 | disequilibrium | haplotype | doublecortin

Hereditary hearing loss that begins early in life may be traced to a gene on chromosome 1p. Researchers studied a large Indonesian family with hereditary, progressive deafness. DNA samples were analyzed from 15 family members with hearing loss. A genetic-linkage analysis was performed to pinpoint the location of the gene for deafness. The gene was localized between D1S211 and D1S201 on chromosome 1p. Linkage analysis was then performed in American and Dutch families with hereditary hearing loss to determine if the same region on chromosome 1p was the location of the gene for deafness. In the American family, the gene was positioned on D1S255 on chromosome 1p. In the Dutch family, the gene for deafness was not located in the suspected region on chromosome 1p. Because the Indonesian and American families are of different ethnic groups, researchers suspect that the gene that causes deafness on chromosome 1p may be responsible for hereditary hearing loss in other families.