Variants of the KIAA0319 gene have been associated with developmental dyslexia.[3]
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%.[1]
An NIDCD-supported investigator recently has identified a mutation in a gene on chromosome 6, called the KIAA0319 gene, that appears to play a key role in Specific Language Impairment.[4]
Function
File:KIAA0319 Protein20154-300.jpgOver-expression of C-terminally myc-tagged KIAA0319 protein in transiently transfected 293T cells, showing plasma membrane localization. Detection with monoclonal anti-myc 9E10.
The KIAA0319 protein is expressed on the cell membrane and may be involved in neuronal migration. Furthermore, KIAA0319 follows a clathrin-mediated endocytic pathway[5]
↑Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (April 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from the brain which can code for large proteins in vitro". DNA Res. 4 (2): 141–50. doi:10.1093/dnares/4.2.141. PMID9205841.
Ozçelik T, Porteus MH, Rubenstein JL, Francke U (1992). "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. doi:10.1016/0888-7543(92)90031-M. PMID1354641.
Cardon LR, Smith SD, Fulker DW, et al. (1994). "Quantitative trait locus for reading disability on chromosome 6". Science. 266 (5183): 276–9. doi:10.1126/science.7939663. PMID7939663.
Nagase T, Ishikawa K, Nakajima D, et al. (1997). "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 Res. 4 (2): 141–50. doi:10.1093/dnares/4.2.141. PMID9205841.
Mungall AJ, Palmer SA, Sims SK, et al. (2003). "The DNA sequence and analysis of human chromosome 6". Nature. 425 (6960): 805–11. doi:10.1038/nature02055. PMID14574404.
Paracchini S, Thomas A, Castro S, et al. (2006). "The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration". Hum. Mol. Genet. 15 (10): 1659–66. doi:10.1093/hmg/ddl089. PMID16600991.
Luciano M, Lind PA, Duffy DL, et al. (2007). "A haplotype spanning KIAA0319 and TTRAP is associated with normal variation in reading and spelling ability". Biol. Psychiatry. 62 (7): 811–7. doi:10.1016/j.biopsych.2007.03.007. PMID17597587.
Velayos-Baeza A, Toma C, da Roza S, et al. (2008). "Alternative splicing in the dyslexia-associated gene KIAA0319". Mamm. Genome. 18 (9): 627–34. doi:10.1007/s00335-007-9051-3. PMID17846832.
