X-linked intellectual disability

X-linked intellectual disability
Classification and external resources
MeSH D038901

X-linked intellectual disability (previously known as X-linked mental retardation) refers to forms of intellectual disability which are specifically associated with X-linked recessive inheritance.

As with most X-linked disorders, males are more heavily affected than females.[1] Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.

Unlike many other types of intellectual disability, the genetics of these conditions are relatively well understood.[2][3] It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.[4]

X-linked intellectual disability accounts for ~16% of all cases of intellectual disability in males.


Several X-linked syndromes include intellectual disability as part of the presentation. These include Coffin–Lowry syndrome, MASA syndrome, X-linked alpha thalassemia mental retardation syndrome, and mental retardation and microcephaly with pontine and cerebellar hypoplasia.

List of genes

Following is a list of genes located on the X chromosome and linked to intellectual disability. There are also several loci that have not been associated with a specific gene.


  1. "Fragile X Syndrome - X-linked Mental Retardation and Macroorchidism". International Birth Defect Information Systems. Retrieved 2010-12-10.
  2. Ropers, H. -H.; Hamel, B. C. J. (2005). "X-linked mental retardation". Nature Reviews Genetics. 6 (1): 46–57. doi:10.1038/nrg1501. PMID 15630421.
  3. Lugtenberg, D.; Veltman, J. A.; Van Bokhoven, H. (2007). "High-resolution genomic microarrays for X-linked mental retardation". Genetics in Medicine. 9 (9): 560–565. doi:10.1097/GIM.0b013e318149e647. PMID 17873643.
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  6. Abidi FE, Holinski-Feder E, Rittinger O, Kooy F, Lubs HA, Stevenson RE, Schwartz CE (Jun 2002). "A novel 2 bp deletion in the TM4SF2 gene is associated with MRX58". J Med Genet. 39 (6): 430–3. doi:10.1136/jmg.39.6.430. PMC 1735161Freely accessible. PMID 12070254.
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  10. Franze A, Archidiacono N, Rocchi M, Marino M, Grimaldi G (Jul 1991). "Isolation and expression analysis of a human zinc finger gene (ZNF41) located on the short arm of the X chromosome". Genomics. 9 (4): 728–36. doi:10.1016/0888-7543(91)90367-N. PMID 2037297.
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  12. Ramser J, Winnepenninckx B, Lenski C, Errijgers V, Platzer M, Schwartz CE, Meindl A, Kooy RF (Sep 2004). "A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9)". J Med Genet. 41 (9): 679–83. doi:10.1136/jmg.2004.019000. PMC 1735884Freely accessible. PMID 15342698.
  13. Guy, MP & Phizicky, EM. (Oct 2014). "Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes". rna. 21: 61–74. doi:10.1261/rna.047639.114. PMID 25404562.
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  15. Bienvenu T, Poirier K, Friocourt G, et al. (2003). "ARX, a novel Prd-class-homeobox gene highly expressed in the telencephalon, is mutated in X-linked mental retardation". Hum. Mol. Genet. 11 (8): 981–91. doi:10.1093/hmg/11.8.981. PMID 11971879.
  16. Jensen LR (2005). "Mutations in the JARID1C Gene, Which Is Involved in Transcriptional Regulation and Chromatin Remodeling, Cause X-Linked Mental Retardation". Am. J. Hum. Genet. 76 (2): 227–36. doi:10.1086/427563. PMC 1196368Freely accessible. PMID 15586325.
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  19. Stettner GM, Shoukier M, Höger C, Brockmann K, Auber B (August 2011). "Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion". Am. J. Med. Genet. A. 155A (8): 2003–7. doi:10.1002/ajmg.a.34122. PMID 21739600.
  20. Melko M, Douguet D, Bensaid M, et al. (May 2011). "Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability". Hum. Mol. Genet. 20 (10): 1873–85. doi:10.1093/hmg/ddr069. PMID 21330300.
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