Non‐syndromic X linked intellectual disability: Current knowledge in light of the recent advances in molecular and functional studies

• Published in: Clinical genetics 2020-05, Vol.97 (5), p.677-687
• Main Authors: Tejada, María Isabel, Ibarluzea, Nekane
• Format: Article
• Language: English
• Subjects: FMR1 gene; FMR1 protein; Fragile X syndrome; Genes; Hybridization; Intellectual disabilities; Next-generation sequencing; non‐syndromic‐intellectual disability; Phenotypes; syndromic‐intellectual disability; X‐linked intellectual disability
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13698

Since the discovery of the FMR1 gene and the clinical and molecular characterization of Fragile X Syndrome in 1991, more than 141 genes have been identified in the X‐chromosome in these 28 years thanks to applying continuously evolving molecular techniques to X‐linked intellectual disability (XLID) families. In the past decade, array comparative genomic hybridization and next generation sequencing technologies have accelerated gene discovery exponentially. Classically, XLID has been subdivided in syndromic intellectual disability (S‐XLID)—where intellectual disability (ID) is always associated with other recognizable physical and/or neurological features—and non‐specific or non‐syndromic intellectual disability (NS‐XLID) where the only common feature is ID. Nevertheless, new advances on the study of these entities have showed that this classification is not always clear‐cut because distinct variants in several of these XLID genes can result in S‐XLID as well as in NS‐XLID. This review focuses on the current knowledge on the XLID genes involved in non‐syndromic forms, with the emphasis on their pathogenic mechanism, thus allowing the possibility to elucidate why some of them can give both syndromic and non‐syndromic phenotypes.