Clinical findings in individuals with duplication of genes associated with X-linked intellectual disability

Duplication of all genes associated with X-linked intellectual disability (XLID) have been reported but the majority of the duplications include more than one XLID gene. It is exceptional for whole XLID gene duplications to cause the same phenotype as sequence variants or deletions of the same gene. Duplication of PLP1, the gene associated with Pelizaeus-Merzbacher syndrome, is the most notable duplication of this type. More commonly, duplication of XLID genes results in very different phenotypes than sequence alterations or deletions. Duplication of MECP2 is widely recognized as a duplication of this type, but a number of others exist. The phenotypes associated with gene duplications are often milder than those caused by deletions and sequence variants. Among some duplications that are clinically significant, marked skewing of X-inactivation in female carriers has been observed. This report describes the phenotypic consequences of duplication of 22 individual XLID genes, of which 10 are described for the first time. Location of single XLID gene duplications (left) and location of all 164 XLID genes (right).image

Automated summary

Duplication of genes associated with X-linked intellectual disability (XLID) is common but usually involves multiple genes. Whole gene duplications causing the same phenotype as sequence variants or deletions are rare. Phenotypes associated with gene duplications are generally milder than those caused by sequence alterations or deletions. Some clinically significant duplications have been observed to result in significant skewing of X-inactivation in female carriers.