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要旨:
Speech and language impairments that are a primary deficit and have no obvious cause (e.g. a comorbid neurological disorder like autism) are diagnosed as Specific Language Impairment (SLI). SLI
affects 5–8 % of preschool children and represents a lifelong disability associated with an increased risk of behavioural disorders, social problems and literacy deficits. SLI is highly heritable and twin studies indicate a strong genetic basis. Nonetheless, the underlying genetic mechanisms are expected to be multifactorial and, to date, only three risk variants have been identified. One way
to increase the power to detect contributory genetic factors is to study isolated populations derived from relatively recent shared ancestors (founder populations). In 2008, Villanueva described a founder population with a particularly high incidence of SLI (10 times that expected). They inhabit the Robinson Crusoe Island, which lies 677 km to the west of Chile and was colonised in the late 19th century by 8 European and Amerindian families. 77 % of the current island population have a colonising surname and 14 % of marriages involve consanguineous unions. More than 80 % of language impaired individuals can be traced to a pair of founder brothers. This population thus has a short (5-generations) and well documented history and represents a unique resource which could make valuable contributions to the elucidation of genetic mechanisms underpinning SLI. We applied exome sequencing technologies to five language impaired individuals from this population and identified nine nonsynonymous
coding changes or splice site mutations that were present in at least three of the five affected individuals sequenced. Sequencing
of the entire cohort identified a single non-synonymous coding change that was significantly more frequent in cases than controls (genotype frequencies of 46 and 11 % respectively, p = 4.48 9 10-5). We
suggest that this rare coding variant may contribute to the elevated frequency of SLI in this population.
