Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment

• Published in: Journal of speech, language, and hearing research Vol. 63; no. 12; pp. 4046 - 4061
• Main Authors: Andres, Erin M, Earnest, Kathleen Kelsey, Smith, Shelley D, Rice, Mabel L, Raza, Muhammad Hashim
• Format: Journal Article
• Language: English
• Published: United States American Speech-Language-Hearing Association 01.12.2020
• Subjects: Articulation (Speech); Biochemistry; Children; Chromosome Mapping; Chromosomes; Cognitive Development; Communication Disorders; Delayed language acquisition; Delayed Speech; Developmental Delays; Environmental Influences; Expressive Language; Families & family life; Family (Sociological Unit); Gene loci; Genetic aspects; Genetic Disorders; Genetic Predisposition to Disease - genetics; Genetics; Genomics; Genotype & phenotype; Hearing disorders; Hearing Impairments; Hearing loss; Humans; Identification; Identification and classification; Intellectual disabilities; Intelligence Quotient; Intelligence Tests; Language; Language acquisition; Language Aptitude; Language disorders; Language Impairments; Language Skills; Language Tests; Lod Score; Longitudinal Studies; Maturity (Individuals); Methods; Mutation; Nonparametric Statistics; Numbers; Pedigree; Quantitative trait loci; Scientific Research; Short Term Memory; Specific Language Disorder; Specific language impairment; Speech Tests; Standard scores; Teaching Methods; Tests; Twins; Kansas; United States
• ISSN: 1092-4388; 1558-9102
• DOI: 10.1044/2020_JSLHR-20-00102

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.