Dyslexia-associated protein explained

Dyslexia-associated protein KIAA0319 is a protein which in humans is encoded by the KIAA0319 gene.^{[1] [2]}

Clinical significance

Variants of the KIAA0319 gene have been associated with developmental dyslexia.^{[3] [4]} Reading disability, or dyslexia, is a major social, educational and mental health problem. In spite of average intelligence and adequate educational opportunities, 5 to 10% of school children have substantial reading deficits. Twin and family studies have shown a substantial genetic component to this disorder, with heritable variation estimated at 50 to 70%.

Mutations in the gene also more generally appear to play a key role in specific language impairment (SLI).^{[5] [6]}

Function

The KIAA0319 protein is expressed on the cell membrane and may be involved in neuronal migration. Furthermore, KIAA0319 follows a clathrin-mediated endocytic pathway.^[7]

Further reading

• Ozçelik T, Porteus MH, Rubenstein JL, Francke U . DLX2 (TES1), a homeobox gene of the Distal-less family, assigned to conserved regions on human and mouse chromosomes 2 . Genomics . 13 . 4 . 1157–61 . August 1992 . 1354641 . 10.1016/0888-7543(92)90031-M .
• Cardon LR, Smith SD, Fulker DW, Kimberling WJ, Pennington BF, DeFries JC . Quantitative trait locus for reading disability on chromosome 6 . Science . 266 . 5183 . 276–9 . October 1994 . 7939663 . 10.1126/science.7939663 . 1994Sci...266..276C .
• Gayán J, Smith SD, Cherny SS, Cardon LR, Fulker DW, Brower AM, Olson RK, Pennington BF, DeFries JC . Quantitative-trait locus for specific language and reading deficits on chromosome 6p . American Journal of Human Genetics . 64 . 1 . 157–64 . January 1999 . 9915954 . 1377713 . 10.1086/302191 .
• Nakayama M, Kikuno R, Ohara O . Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs . Genome Research . 12 . 11 . 1773–84 . November 2002 . 12421765 . 187542 . 10.1101/gr.406902 .
• Londin ER, Meng H, Gruen JR . A transcription map of the 6p22.3 reading disability locus identifying candidate genes . BMC Genomics . 4 . 1 . 25 . June 2003 . 12834540 . 166143 . 10.1186/1471-2164-4-25 . free .
• Francks C, Paracchini S, Smith SD, Richardson AJ, Scerri TS, Cardon LR, Marlow AJ, MacPhie IL, Walter J, Pennington BF, Fisher SE, Olson RK, DeFries JC, Stein JF, Monaco AP . A 77-kilobase region of chromosome 6p22.2 is associated with dyslexia in families from the United Kingdom and from the United States . American Journal of Human Genetics . 75 . 6 . 1046–58 . December 2004 . 15514892 . 1182140 . 10.1086/426404 .
• Luciano M, Lind PA, Duffy DL, Castles A, Wright MJ, Montgomery GW, Martin NG, Bates TC . A haplotype spanning KIAA0319 and TTRAP is associated with normal variation in reading and spelling ability . Biological Psychiatry . 62 . 7 . 811–7 . October 2007 . 17597587 . 10.1016/j.biopsych.2007.03.007 . 11334660 .
• Velayos-Baeza A, Toma C, da Roza S, Paracchini S, Monaco AP . Alternative splicing in the dyslexia-associated gene KIAA0319 . Mammalian Genome . 18 . 9 . 627–34 . September 2007 . 17846832 . 10.1007/s00335-007-9051-3 . 42549021 .

External links

• KIAA0319 Associations, Experiments, Publications and Clinical Trials

Notes and References

1. Web site: Entrez Gene: KIAA0319 KIAA0319.
2. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro . DNA Research . 4 . 2 . 141–50 . April 1997 . 9205841 . 10.1093/dnares/4.2.141 . free .
3. Cope N, Harold D, Hill G, Moskvina V, Stevenson J, Holmans P, Owen MJ, O'Donovan MC, Williams J . Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia . American Journal of Human Genetics . 76 . 4 . 581–91 . April 2005 . 15717286 . 1199296 . 10.1086/429131 .
4. Paracchini S, Thomas A, Castro S, Lai C, Paramasivam M, Wang Y, Keating BJ, Taylor JM, Hacking DF, Scerri T, Francks C, Richardson AJ, Wade-Martins R, Stein JF, Knight JC, Copp AJ, Loturco J, Monaco AP . 6 . The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration . Human Molecular Genetics . 15 . 10 . 1659–66 . May 2006 . 16600991 . 10.1093/hmg/ddl089 . free . 11858/00-001M-0000-0012-C979-F . free .
5. Rice ML, Smith SD, Gayán J . Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment . Journal of Neurodevelopmental Disorders . 1 . 4 . 264–82 . December 2009 . 19997522 . 2788915 . 10.1007/s11689-009-9031-x .
6. Gibson CJ, Gruen JR . The human lexinome: genes of language and reading . Journal of Communication Disorders . 41 . 5 . 409–20 . 2008 . 18466916 . 2488410 . 10.1016/j.jcomdis.2008.03.003 .
7. Levecque C, Velayos-Baeza A, Holloway ZG, Monaco AP . The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway . American Journal of Physiology. Cell Physiology . 297 . 1 . C160-8 . July 2009 . 19419997 . 2711651 . 10.1152/ajpcell.00630.2008 .