Mapping Chromosomal Loci in Specific Language Impairment: A Pedigree-Focused Approach

Abstract

Specific language impairment (SLI) is characterized by a delay in the mastery of language despite average or above average nonverbal intelligence (IQ). There are multiple assessments used in practice to measure the language abilities of individuals with SLI. Standardized language assessments in conjunction with a measure of nonverbal IQ are the most crucial for distinguishing individuals with and without SLI in research practice. Studies have found that the incidence of SLI in extended relatives of probands is significantly higher than population matched relatives of controls. The heritability estimates of SLI are higher in MZ twins than DZ twins. Both family and twin studies indicate genetic involvement in the transmission of SLI. Previous genetic studies in SLI have found candidate chromosomal loci on 2q24, 6p21, 10q26, 12p13, 21q, and several candidate genes including TM4SF20, NFXL1, CNTNAP2, KIAA0319, CMIP, and ATP2C2 have been implicated in SLI. However, the causes of SLI are not well understood and investigation may benefit from family-based approaches. The current study approached genetic investigation of SLI one pedigree at a time. We report SLI loci on chromosomes 4q, 3p, 6q, 9q, 10q, 12p, 14q and 15q linked with the omnibus standard score categorical phenotype, indicating genetic and phenotypic heterogeneity of SLI. These findings support the discussion of previous hypotheses that SLI is a polygenic disorder, with multiple loci reported in a few of the families included in this report.