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Identifying Genes Responsible for Intellectual Disability in Consanguineous Families

Consanguinity is an important determinant of birth defects including intellectual disability (ID). Consanguineous populations have a relative high prevalence of autosomal recessive forms of intellectual disability (ARID), which constitute a highly heterogeneous group of disorders both in their clinical presentation and in their genetic aetiology. The availability of large cohorts of consanguineous families and the advent of next-generation sequencing techniques is currently accelerating the pace of gene identification in ARID. Because of the extreme heterogeneity, it is anticipated that hundreds of ARID (candidate) genes will be identified in the near future. With this robust progress, the proof of causality of the identified candidate genes is challenging. To this end, genetic recurrence, cellular assays and animal modelling would serve as three non-exclusive strategies, in order to assign causality to a certain gene. Extensive genetic investigations in consanguineous populations will help in reducing the total disease burden through proper genetic counselling. Moreover, such findings will be helpful to elucidate different pathways and further for possible therapeutic interventions.