Intellectual disability genomics: current state, pitfalls and future challenges

BMC Genomics. 2021 Dec 20;22(1):909. doi: 10.1186/s12864-021-08227-4.


Intellectual disability (ID) can be caused by non-genetic and genetic factors, the latter being responsible for more than 1700 ID-related disorders. The broad ID phenotypic and genetic heterogeneity, as well as the difficulty in the establishment of the inheritance pattern, often result in a delay in the diagnosis. It has become apparent that massive parallel sequencing can overcome these difficulties. In this review we address: (i) ID genetic aetiology, (ii) clinical/medical settings testing, (iii) massive parallel sequencing, (iv) variant filtering and prioritization, (v) variant classification guidelines and functional studies, and (vi) ID diagnostic yield. Furthermore, the need for a constant update of the methodologies and functional tests, is essential. Thus, international collaborations, to gather expertise, data and resources through multidisciplinary contributions, are fundamental to keep track of the fast progress in ID gene discovery.

Keywords: Animal and cellular modelling; Genome editing; Intellectual disability; Massive parallel sequencing; Neurodevelopmental disorders; Variant filtering; Variant prioritization.

Publication types

  • Review

MeSH terms

  • Genomics
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics