Genetic factors are an important cause of functional articulation disorder in children. This article reviews some genes and chromosome regions associated with a genetic susceptibility to functional articulation disorders. The forkhead box P2 (FOXP2) gene on chromosome 7 is introduced in details including its structure, expression and function. The relationship between the FOXP2 gene and developmental apraxia of speech is discussed. As a transcription factor, FOXP2 gene regulates the expression of many genes. CNTNAP2 as an important target gene of FOXP2 is a key gene influencing language development. Functional articulation disorder may be developed to dyslexia, therefore some candidate regions and genes related to dyslexia, such as 3p12-13, 15q11-21, 6p22 and 1p34-36, are also introduced. ROBO1 gene in 3p12.3, ZNF280D gene, TCF12 gene, EKN1 gene in 15q21, and KIAA0319 gene in 6p22 have been candidate genes for the study of functional articulation disorder.
ZHAO Yun-Jing, MA Hong-Wei.
Molecular genetics of functional articulation disorder in children[J]. Chinese Journal of Contemporary Pediatrics. 2012, 14(4): 316-320
［2］Ho CS, Leung MT, Cheung H. Early difficulties of Chinese preschoolers at familial risk for dyslexia: deficits in oral language, phonological processing skills, and print-related skills［J］. Dyslexia, 2011, 17(2):143-164.
［5］Felsenfeld S, McGue M, Broen PA. Familial aggregation of phonological disorders: results from a 28-year follow-up［J］. J Speech Hear Res, 1995, 38(5): 1091-1107.
［6］Forrest K. Diagnostic criteria of developmental apraxia of speech used by clinical speech-language pathologists［J］. Am J Speech Lang Pathol, 2003, 12(3): 376-380.
［7］Hurst JA, Baraitser M, Auger E, Graham F, Norell S. An extended family with a dominantly inherited speech disorder［J］. Dev Med Child Neurol, 1990, 32(4):352-355.
［8］Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP. A forkhead-domain gene is mutated in a severe speech and language disorder［J］. Nature, 2001, 413(6855): 519-523.
［9］Vernes SC, Nicod J, Elahi FM, Coventry JA, Kenny N, Coupe AM, et al. Functional genetic analysis of mutations implicated in a human speech and language disorder［J］. Hum Mol Genet, 2006, 15(21): 3154-3167.
［10］Fisher SE, Marcus GF. The eloquent ape: genes, brains and the evolution of language［J］. Nat Rev Genet, 2006, 7(1): 9-20.
［11］Groszer M, Keays DA, Deacon RM, de Bono JP, Prasad-Mulcare S, Gaub S, et al. Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits［J］. Curr Biol, 2008, 18(5): 354-362.
［12］Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovi'c D, et al. Functional and evolutionary insights into human brain development through global transcriptome analysis［J］. Neuron, 2009, 62(4): 494-509.
［13］Spiteri E, Konopka G, Coppola G, Bomar J, Oldham M, Ou J, et al. Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain［J］. Am J Hum Genet, 2007, 81(6): 1144-1157.
［14］Newbury DF, Fisher SE, Monaco AP. Recent advances in the genetics of language impairment［J］. Genome Med, 2010, 2(1):6.
［15］Vernes SC, Fisher SE.Unravelling neurogenetic networks implicated in developmental language disorders［J］. Biochem Soc Trans, 2009, 37(Pt 6): 1263-1269.
［16］Konopka G, Bomar JM, Winden K, Coppola G, Jonsson ZO, Gao F, et al. Human-specific transcriptional regulation of CNS development genes by FOXP2［J］. Nature, 2009, 462(7270): 213-217.
［17］Vernes SC, Spiteri E, Nicod J, Groszer M, Taylor JM, Davies KE, et al. High-throughput analysis of promoter occupancy reveals direct neural targets of FOXP2, a gene mutated in speech and language disorders［J］. Am J Hum Genet, 2007, 81(6): 1232-1250.
［18］Vernes SC, Newbury DF, Abrahams BS, Winchester L, Nicod J, Groszer M, et al. A functional genetic link between distinct developmental language disorders［J］. N Engl J Med, 2008, 359(22): 2337-2345.
［19］Alarcón M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene［J］. Am J Hum Genet, 2008, 82(1): 150-159.
［20］Abrahams BS, Tentler D, Perederiy JV, Oldham MC, Coppola G, Geschwind DH. Genome-wide analyses of human perisylvian cerebral cortical patterning［J］. Proc Natl Acad Sci U S A, 2007, 104(45): 17849-17854.
［21］Peter B, Raskind WH, Matsushita M, Lisowski M, Vu T, Berninger VW, et al. Replication of CNTNAP2 association with nonword repetition and support for FOXP2 association with timed reading and motor activities in a dyslexia family sample［J］. J Neurodev Disord, 2011, 3(1): 39-49.
［22］Whitehouse AJ, Bishop DV, Ang QW, Pennell CE, Fisher SE. CNTNAP2 variants affect early language development in the general population［J］.Genes Brain Behav, 2011, 10(4): 451-456.
［23］Vernes SC, MacDermot KD, Monaco AP, Fisher SE.Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia［J］. Eur J Hum Genet, 2009, 17(10): 1354-1358.
［24］MacDermot KD, Bonora E, Sykes N, Coupe AM, Lai CS, Vernes SC, et al. Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits［J］. Am J Hum Genet, 2005, 76(6): 1074-1080.
［25］Feuk L, Kalervo A, Lipsanen-Nyman M, Skaug J, Nakabayashi K, Finucane B, et al. Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia［J］. Am J Hum Genet, 2006, 79(5): 965-972.
［26］Zeesman S, Nowaczyk MJ, Teshima I, Roberts W, Cardy JO, Brian J, et al. Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2［J］. Am J, Med Genet A, 2006, 140(5): 509-514.
［27］Lennon PA, Cooper ML, Peiffer DA, Gunderson KL, Patel A, Paters S, et al. Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review［J］. Am J Med Genet A, 2007, 143A(8): 791-798.
［28］Wilcke A, Ligges C, Burkhardt J, Alexander M, Wolf C, Quente E, et al. Imaging genetics of FOXP2 in dyslexia［J］. Eur J Hum Genet, 2012, 20(2): 224-229.
［29］Zhao Y, Ma H, Wang Y, Gao H, Xi C, Hua T, et al. Association between FOXP2 gene and speech sound disorder in Chinese population［J］.Psychiatry Clin Neurosci, 2010, 64(5): 565-573.
［30］Nopola-Hemmi J, Myllyluoma B, Haltia T, Taipale M, Ollikainen V, Ahonen T, et al. A dominant gene for developmental dyslexia on chromosome 3［J］. J Med Genet, 2001, 38(10): 658-664.
［31］Stein CM, Schick JH, Gerry Taylor H, Shriberg LD, Millard C, Kundtz-Kluge A. Pleiotropic effects of a chromosome 3 locus on speech-sound disorder and reading［J］. Am J Hum Genet, 2004, 74(2): 283-297.
［32］Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, Eklund R, Nopola-Hemmi J, Kaariainen H, et al. The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia［J］.PLoS Genet, 2005, 1(4): e50.
［33］Bates TC, Luciano M, Medland SE, Montgomery GW, Wright MJ, Martin NG.Genetic variance in a component of the language acquisition device: ROBO1 polymorphisms associated with phonological buffer deficits［J］. Behav Genet, 2011, 41(1): 50-57.
［34］Butler MG, Bittel DC, Kibiryeva N, Talebizadeh Z, Thompson T. Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy［J］. Pediatrics, 2004, 113(3 Pt 1): 565-573.
［35］Fisher SE, DeFries JC. Developmental dyslexia: genetic dissection of a complex cognitive trait［J］. Nat Rev Neurosci, 2002, 3(10): 767-780.
［36］Buonincontri R, Bache I, Silahtaroglu A, Elbro C, Nielsen AM, Ullmann R, et al. A cohort of balanced reciprocal translocations associated with dyslexia: identification of two putative candidate genes at DYX1［J］.Behav Genet, 2011, 41(1): 125-133.
［37］Wigg KG, Couto JM, Feng Y, Anderson B, Cate-Carter TD, Macciardi F, et al. Support for EKN1 as the susceptibility locus for dyslexia on 15q21［J］.Mol Psychiatry, 2004, 9(12): 1111-1121.
［39］Stein CM, Millard C, Kluge A, Miscimarra LE, Cartier KC, Freebairn LA, et al. Speech sound disorder influenced by a locus in 15q14 region［J］. Behav Genet, 2006, 36(6): 858-868.
［40］Venkatesh SK, Siddaiah A, Padakannaya P, Ramachandra NB. An examination of candidate gene SNPs for dyslexia in an Indian sample［J］.Behav Genet, 2011, 41(1): 105-109.
［41］Paracchini S, Steer CD, Buckingham LL, Morris AP, Ring S, Scerri T, et al, Association of the KIAA0319 dyslexia susceptibility gene with reading skills in the general population［J］.Am J Psychiatry, 2008, 165(12): 1576-1584.
［42］Elbert A, Lovett MW, Cate-Carter T, Pitch A, Kerr EN, Barr CL. Genetic variation in the KIAA0319 5' region as a possible contributor to dyslexia［J］.Behav Genet, 2011, 41(1): 77-89.
［43］Lind PA, Luciano M, Wright MJ, Montgomery GW, Martin NG, Bates TC. Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample［J］.Eur J Hum Genet, 2010, 18(6): 668-673.
［44］Schumacher J, Anthoni H, Dahdouh F, K-nig IR, Hillmer AM, Kluck N, et al. Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia［J］.Am J Hum Genet, 2006, 78(1): 52-62.
［45］Meng H, Powers NR, Tang L, Cope NA, Zhang PX, Fuleihan R, et al. A dyslexia-associated variant in DCDC2 changes gene expression［J］.Behav Genet, 2011, 41(1): 58-66.
［46］Miscimarra L, Stein C, Millard C, Kluge A, Cartier K, Freebairn L, et al. Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region［J］. Hum Hered, 2007, 63(1): 47-58.
［47］Couto JM, Gomez L, Wigg K, Cate-Carter T, Archibald J, Anderson B, et al. The KIAA0319-like (KIAA0319L) gene on chromosome 1p34 as a candidate for reading disabilities［J］. J Neurogenet, 2008, 22(4): 295-313.
