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Review
. 2012 Apr 6;90(4):579-90.
doi: 10.1016/j.ajhg.2012.02.018.

Fragile X and X-linked intellectual disability: four decades of discovery

Herbert A Lubs  1 , Roger E Stevenson, Charles E Schwartz
Affiliations
Review

Fragile X and X-linked intellectual disability: four decades of discovery

Herbert A Lubs et al. Am J Hum Genet. .

Abstract

X-Linked intellectual disability (XLID) accounts for 5%-10% of intellectual disability in males. Over 150 syndromes, the most common of which is the fragile X syndrome, have been described. A large number of families with nonsyndromal XLID, 95 of which have been regionally mapped, have been described as well. Mutations in 102 X-linked genes have been associated with 81 of these XLID syndromes and with 35 of the regionally mapped families with nonsyndromal XLID. Identification of these genes has enabled considerable reclassification and better understanding of the biological basis of XLID. At the same time, it has improved the clinical diagnosis of XLID and allowed for carrier detection and prevention strategies through gamete donation, prenatal diagnosis, and genetic counseling. Progress in delineating XLID has far outpaced the efforts to understand the genetic basis for autosomal intellectual disability. In large measure, this has been because of the relative ease of identifying families with XLID and finding the responsible mutations, as well as the determined and interactive efforts of a small group of researchers worldwide.

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Figures

Figure 1
Figure 1
Genes with Identified Mutations that Cause Syndromal XLID with Chromosomal Band Location
Figure 2
Figure 2
Location of Genes with Mutations that Cause Nonsyndromal XLID Twenty-two genes shown on the left of the chromosome with solid arrows cause nonsyndromal XLID only. Numbers in parentheses adjacent to the gene symbols are assigned MRX numbers. Seventeen genes shown on the right of the chromosome with open arrows cause both syndromal and nonsyndromal XLID.
Figure 3
Figure 3
Approximate Linkage Limits for XLID Syndromes for which the Genes Have Not Been Identified
Figure 4
Figure 4
The Year and Methodology Used to Identify Genes Associated with XLID The following abbreviations are used: Exp-Arr = expression microarray. MCGH = genomic microarray. X-seq = gene sequencing. Mol-Fu = follow up of a known molecular pathway. L-can = candidate gene testing within a linkage interval. Chr-rea = positional cloning based on a chromosome rearrangement. Met-Fu = follow up of a known metabolic pathway.
Figure 5
Figure 5
Location of Segmental Duplications Associated with Syndromal or Nonsyndromal XLID
See this image and copyright information in PMC

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