Abstract
PurposeSpecific 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.MethodWe 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.ResultsA 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.ConclusionsThese 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.Supplemental Material https://doi.org/10.23641/asha.13203218
Highlights
Most children acquire language without any formal instruction
Six probands with Specific language impairment (SLI) and their family members were included in genome-wide parametric linkage analysis, and the highest logarithm of odds (LOD) scores were compared with the maximum estimated LOD (ELOD)
This agrees with visual inspection of the mode of inheritance in Family 387, which shows the possibility of sex-linked recessive inheritance
Summary
Most children acquire language without any formal instruction. Contrary to common expectations, language does not come to all children. The estimated prevalence of SLI (excluding children with low/borderline normal nonverbal IQ) is 7% in the United States (Tomblin et al, 1997), an Family aggregation and twin studies provide evidence that the language acquisition difficulties children with SLI experience are inherited (Bishop et al, 2006, 1995; Bishop & Hayiou-Thomas, 2008; Rice et al, 1998, 2020, 2018; Tallal et al, 2001). Twin studies of individuals with and without SLI have revealed strong heritability estimates for multiple speech and language phenotypes in dizygotic and monozygotic twins (Bishop & Hayiou-Thomas, 2008; Rice et al, 2020, 2018).
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