Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2013

Open Access 01-12-2013 | Research

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech

Authors: Elizabeth A Worthey, Gordana Raca, Jennifer J Laffin, Brandon M Wilk, Jeremy M Harris, Kathy J Jakielski, David P Dimmock, Edythe A Strand, Lawrence D Shriberg

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2013

Login to get access

Abstract

Background

Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS.

Methods

As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker’s speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development.

Results

Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent.

Conclusions

Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of this pediatric motor speech disorder with multiple genes, pathways and complex interactions. We also submit that our findings illustrate the potential use of WES for both gene identification and case-by-case clinical diagnostics in pediatric motor speech disorders.
Literature
1.
Bras J, Guerreiro R, Hardy J: Use of next-generation sequencing and other whole-genome strategies to dissect neurological disease. Nat Rev Neurosci. 2012, 13: 453-464.PubMedCrossRef
2.
Gardy JL: Investigation of disease outbreaks with genome sequencing. Lancet Infect Dis. 2013, 13: 101-102. 10.1016/S1473-3099(12)70295-5.PubMedCrossRef
3.
Hastings R, de Wert G, Fowler B, Krawczak M, Vermeulen E, Bakker E, Borry P, Dondorp W, Nijsingh N, Barton D, Schmidtke J, van El CG, Vermeesch J, Stol Y, Howard HC, Cornel MC: The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe. Eur J Hum Genet. 2012, 20: 911-916. 10.1038/ejhg.2012.56.PubMedCentralPubMedCrossRef
4.
5.
Ku CS, Polychronakos C, Tan EK, Naidoo N, Pawitan Y, Roukos DH, Mort M, Cooper DN: A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease. Mol Psychiatry. 2013, 18: 141-153. 10.1038/mp.2012.58.PubMedCrossRef
6.
7.
Shapiro B, Hofreiter M: Analysis of ancient human genomes: using next generation sequencing, 20-fold coverage of the genome of a 4,000-year-old human from Greenland has been obtained. Bioessays. 2010, 32: 388-391. 10.1002/bies.201000026.PubMedCrossRef
8.
9.
Shriberg LD: State of the Art in CAS Diagnostic Marker Research. 2013, Atlanta, GA, USA: Review paper presented at the Childhood Apraxia of Speech Association of North America Speech Research Symposium
10.
van der Merwe A: A theoretical framework for the characterization of pathological speech sensorimotor control. Clinical Management of Sensorimotor Speech Disorders. Edited by: McNeil MR. 2009, New York: Thieme Medical Publishers, 3-18. 2
11.
Shriberg LD: A neurodevelopmental framework for research in childhood apraxia of speech. Speech Motor Control: New Developments in Basic and Applied Research. Edited by: Maassen B, van Lieshout P. 2010, Oxford: Oxford University Press, 259-270.CrossRef
12.
The Royal College of Speech & Language Therapists (RCSLT): RCSLT Policy Statement on Developmental Verbal Dyspraxia. 2011, London: Author
13.
Duffy JR: Motor Speech Disorders: Substrates, Differential Diagnosis, and Management. 2005, St Louis, MO: Mosby, 2
14.
Shriberg LD, Lohmeier HL, Strand EA, Jakielski KJ: Encoding, memory, and transcoding deficits in childhood apraxia of speech. Clin Linguist Phonet. 2012, 26: 445-482. 10.3109/02699206.2012.655841.CrossRef
15.
Duffy JR, Josephs KA: The diagnosis and understanding of apraxia of speech: why including neurodegenerative etiologies may be important. J Speech Lang Hear Res. 2012, 55: S1518-S1522. 10.1044/1092-4388(2012/11-0309).PubMedCentralPubMedCrossRef
16.
Lai CSL, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP: A forkhead-domain gene is mutated in a severe speech and language disorder. Nature. 2001, 413: 519-523. 10.1038/35097076.PubMedCrossRef
17.
Spiteri E, Konopka G, Coppola G, Bomar J, Oldham M, Ou J, Vernes SC, Fisher SE, Ren B, Geschwind DH: Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain. Am J Hum Genet. 2007, 81: 1144-1157. 10.1086/522237.PubMedCentralPubMedCrossRef
18.
Vernes SC, Fisher SE: Unravelling neurogenetic networks implicated in developmental language disorders. Biochem Soc Trans. 2009, 37: 1263-1269. 10.1042/BST0371263.PubMedCrossRef
19.
Rice GM, Raca G, Jakielski KJ, Laffin JJ, Iyama-Kurtycz CM, Hartley SL, Sprague RE, Heintzelman AT, Shriberg LD: Phenotype of FOXP2 haploinsufficiency in a mother and son. Am J Med Genet A. 2012, 158A: 174-181. 10.1002/ajmg.a.34354.PubMedCentralPubMedCrossRef
20.
Tomblin JB, O’Brien M, Shriberg LD, Williams C, Murray J, Patil S, Bjork J, Anderson S, Ballard K: Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2. J Speech Lang Hear Res. 2009, 52: 1157-1174. 10.1044/1092-4388(2009/07-0162).PubMedCentralPubMedCrossRef
21.
Lennon PA, Cooper ML, Peiffer DA, Gunderson KL, Patel A, Peters S, Cheung SW, Bacino CA: Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review. Am J Med Genet A. 2007, 143A: 791-798. 10.1002/ajmg.a.31632.PubMedCrossRef
22.
Palka C, Alfonsi M, Mohn A, Cerbo R, Guanciali Franchi P, Fantasia D, Morizio E, Stuppia L, Calabrese G, Zori R, Chiarelli F, Palka G: Mosaic 7q31 deletion involving FOXP2 gene associated with language impairment. Pediatrics. 2012, 129: e183-e188. 10.1542/peds.2010-2094.PubMedCrossRef
23.
Zeesman S, Nowaczyk MJ, Teshima I, Roberts W, Cardy JO, Brian J, Senman L, Feuk L, Osborne LR, Scherer SW: Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2. Am J Med Genet A. 2006, 140A: 509-514. 10.1002/ajmg.a.31110.CrossRef
24.
Zilina O, Reimand T, Zjablovskaja P, Männik K, Männamaa M, Traat A, Puusepp-Benazzouz H, Kurg A, Ounap K: Maternally and paternally inherited deletion of 7q31 involving the FOXP2 gene in two families. Am J Med Genet A. 2012, 158A: 254-256. 10.1002/ajmg.a.34378.PubMedCrossRef
25.
Shriberg LD, Ballard KJ, Tomblin JB, Duffy JR, Odell KH, Williams CA: Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2. J Speech Lang Hear Res. 2006, 49: 500-525. 10.1044/1092-4388(2006/038).PubMedCrossRef
26.
Morgan A, Liégeois F, Vargha-Khadem F: Motor speech profile in relation to site of brain pathology: a developmental perspective. Speech Motor Control: New Developments in Basic and Applied Research. Edited by: Maassen B, van Lieshout P. 2010, Oxford: Oxford University Press, 95-115.CrossRef
27.
Turner SJ, Hildebrand MS, Block S, Damiano J, Fahey M, Reilly S, Bahlo M, Scheffer IE, Morgan AT: Small intragenic deletion in FOXP2 associated with childhood apraxia of speech and dysarthria. Am J Med Genet A. 2013, 161: 2321-2326. 10.1002/ajmg.a.36055.CrossRef
28.
29.
Laffin JJS, Raca G, Jackson CA, Strand EA, Jakielski KJ, Shriberg LD: Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization. Genet Med. 2012, 14: 928-936. 10.1038/gim.2012.72.PubMedCentralPubMedCrossRef
30.
MacDermot KD, Bonora E, Sykes N, Coupe AM, Lai CS, Vernes SC, Vargha-Khadem F, McKenzie F, Smith RL, Monaco AP, Fisher SE: Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. Am J Hum Genet. 2005, 76: 1074-1080. 10.1086/430841.PubMedCentralPubMedCrossRef
31.
32.
Feuk L, Kalervo A, Lipsanen-Nyman M, Skaug J, Nakabayashi K, Finueane B, Hartung D, Innes M, Kerem B, Nowaczyk MJ, Rivlin J, Roberts W, Senman L, Summers A, Szatmari P, Wong V, Vincent JB, Zeesman S, Osborne LR, Cardy JO, Kere J, Scherer SW, Hannula-Jouppi K: Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia. Am J Hum Genet. 2006, 79: 965-972. 10.1086/508902.PubMedCentralPubMedCrossRef
33.
Fisher SE: Building bridges between genes, brains and language. Birdsong, Speech and Language: Exploring the Evolution of Mind and Brain. Edited by: Bolhuis JJ, Everaert M. 2013, Cambridge, MA: MIT Press, 425-454.
34.
Fisher SE, Marcus GF: The eloquent ape: genes, brains and the evolution of language. Nat Rev Genet. 2006, 7: 9-20.PubMedCrossRef
35.
Fisher SE, Scharrf C: FOXP2 as a molecular window into speech and language. Trends Genet. 2009, 25: 166-177. 10.1016/j.tig.2009.03.002.PubMedCrossRef
36.
37.
Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA: Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. J Neurosci. 2004, 24: 3152-3163. 10.1523/JNEUROSCI.5589-03.2004.PubMedCrossRef
38.
French CA, Groszer M, Preece C, Coupe AM, Rajewsky K, Fisher SE: Generation of mice with a conditional Foxp2 null allele. Genesis. 2007, 45: 440-446. 10.1002/dvg.20305.PubMedCentralPubMedCrossRef
39.
Fujita E, Tanabe Y, Shiota A, Ueda M, Suwa K, Momoi MY, Momoi T: Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells. Proc Natl Acad Sci U S A. 2008, 105: 3117-3122. 10.1073/pnas.0712298105.PubMedCentralPubMedCrossRef
40.
Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD: Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci U S A. 2005, 102: 9643-9648. 10.1073/pnas.0503739102.PubMedCentralPubMedCrossRef
41.
Alarcón M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH, Nelson SF, Cantor RM, Geschwind DH: Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet. 2008, 82: 150-159. 10.1016/j.ajhg.2007.09.005.PubMedCentralPubMedCrossRef
42.
Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, Sonnenblick LI, Gruver R, Almajano J, Bragin A, Golshani P, Trachtenberg JT, Peles E, Geschwind DH: Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. 2011, 147: 235-246. 10.1016/j.cell.2011.08.040.PubMedCentralPubMedCrossRef
43.
Gregor A, Albrecht B, Bader I, Bijlsma EK, Ekici AB, Engels H, Hackmann K, Horn D, Hoyer J, Klapecki J, Kohlhase J, Maystadt I, Nagl S, Prott E, Tinschert S, Ullmann R, Wohlleber E, Woods G, Reis A, Rauch A, Zweier C: Expanding the clinical spectrum associated with defects in CNTNAP2 and NRXN1. BMC Med Genet. 2011, 12: 106-10.1186/1471-2350-12-106.PubMedCentralPubMedCrossRef
44.
Zweier C, de Jong EK, Zweier M, Orrico A, Ousager LB, Collins AL, Bijlsma EK, Oortveld MA, Ekici AB, Reis A, Schenck A, Rauch A: CNTNAP2 and NRXN1 are mutated in autosomal-recessive Pitt-Hopkins-like mental retardation and determine the level of a common synaptic protein in Drosophila. Am J Hum Genet. 2009, 85: 655-666. 10.1016/j.ajhg.2009.10.004.PubMedCentralPubMedCrossRef
45.
Arking DE, Cutler DJ, Brune CW, Teslovich TM, West K, Ikeda M, Rea A, Guy M, Lin S, Cook EH, Chakravarti A: A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet. 2008, 82: 160-164. 10.1016/j.ajhg.2007.09.015.PubMedCentralPubMedCrossRef
46.
Poot M, Beyer V, Schwaab I, Damatova N, Van’t Slot R, Prothero J, Holder SE, Haaf T: Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder. Neurogenetics. 2010, 11: 81-89. 10.1007/s10048-009-0205-1.PubMedCrossRef
47.
Vernes SC, Newbury DF, Abrahams BS, Winchester L, Nicod J, Groszer M, Alarcón M, Oliver PL, Davies KE, Geschwind DH, Monaco AP, Fisher SE: A functional genetic link between distinct developmental language disorders. N Engl J Med. 2008, 359: 2337-2345. 10.1056/NEJMoa0802828.PubMedCentralPubMedCrossRef
48.
Whitehouse AJ, Bishop DV, Ang QW, Pennell CE, Fisher SE: CNTNAP2 variants affect early language development in the general population. Genes Brain Behav. 2011, 10: 451-456. 10.1111/j.1601-183X.2011.00684.x.PubMedCentralPubMedCrossRef
49.
Rodenas-Cuadrado P, Ho J, Vernes SC: Shining a light on CNTNAP2: complex functions to complex disorders. Eur J Hum Genet. in press. doi:10.1038/ejhg.2013.100
50.
O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE: Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011, 43: 585-589. 10.1038/ng.835.PubMedCentralPubMedCrossRef
51.
Caylak E: A review of association and linkage studies for genetical analyses of learning disorders. Am J Med Genet B Neuropsychiatr Genet. 2007, 144B: 923-943. 10.1002/ajmg.b.30537.PubMedCrossRef
52.
Graham SA, Fisher SE: Decoding the genetics of speech and language. Curr Opin Neurobiol. 2013, 23: 43-51. 10.1016/j.conb.2012.11.006.PubMedCrossRef
53.
Kang C, Drayna D: Genetics of speech and language disorders. Annu Rev Genomics Hum Genet. 2011, 12: 145-164. 10.1146/annurev-genom-090810-183119.PubMedCrossRef
54.
Pinel P, Fauchereau F, Moreno A, Barbot A, Lathrop M, Zelenika D, Le Bihan D, Poline JB, Bourgeron T, Dehaene S: Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions. J Neurosci. 2012, 32: 817-825. 10.1523/JNEUROSCI.5996-10.2012.PubMedCrossRef
55.
56.
Shriberg LD, Potter NL, Strand EA: Prevalence and phenotype of childhood apraxia of speech in youth with galactosemia. J Speech Lang Hear Res. 2011, 54: 487-519. 10.1044/1092-4388(2010/10-0068).PubMedCentralPubMedCrossRef
57.
Carr CW, Moreno-De-Luca D, Parker C, Zimmerman HH, Ledbetter N, Martin CL, Dobyns WB, Abdul-Rahman OA: Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency. Eur J Hum Genet. 2010, 18: 1216-1220. 10.1038/ejhg.2010.96.PubMedCentralPubMedCrossRef
58.
Horn D, Kapeller J, Rivera-Brugués N, Moog U, Lorenz-Depiereux B, Eck S, Hempel M, Wagenstaller J, Gawthrope A, Monaco AP, Bonin M, Riess O, Wohlleber E, Illig T, Bezzina CR, Franke A, Spranger S, Villavicencio-Lorini P, Seifert W, Rosenfeld J, Klopocki E, Rappold GA, Strom TM: Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum Mutat. 2010, 31: E1851-E1860. 10.1002/humu.21362.PubMedCentralPubMedCrossRef
59.
Pariani MJ, Spencer A, Graham JM, Rimoin DL: A 785 kb deletion of 3p14.1p13, including the FOXP1 gene, associated with speech delay, contractures, hypertonia and blepharophimosis. Eur J Med Genet. 2009, 52: 123-127. 10.1016/j.ejmg.2009.03.012.PubMedCentralPubMedCrossRef
60.
Newbury DF, Mari F, Sadighi Akha E, MacDermot KD, Canitano R, Monaco AP, Taylor JC, Renieri A, Fisher SE, Knight SJ: Dual copy number variants involving 16p11 and 6q22 in a case of childhood apraxia of speech and pervasive developmental disorder. Eur J Hum Genet. 2013, 21: 361-365. 10.1038/ejhg.2012.166.PubMedCentralPubMedCrossRef
61.
Raca G, Baas BS, Kirmani S, Laffin JJ, Jackson CA, Strand EA, Jakielski KJ, Shriberg LD: Childhood apraxia of speech (CAS) in two patients with 16p11.2 microdeletion syndrome. Eur J Med Genet. 2013, 21: 455-459.
62.
Osborne LR, Mervis CB: Rearrangements of the Williams-Beuren syndrome locus: molecular basis and implications for speech and language development. Expert Rev Mol Med. 2007, 9: 1-16.PubMedCentralPubMedCrossRef
63.
Somerville MJ, Mervis CB, Young EJ, Seo EJ, del Campo M, Bamforth S, Peregrine E, Loo W, Lilley M, Pérez-Jurado LA, Morris CA, Scherer SW, Osborne LR: Severe expressive-language delay related to duplication of the Williams-Beuren locus. N Engl J Med. 2005, 353: 1694-1701. 10.1056/NEJMoa051962.PubMedCentralPubMedCrossRef
64.
Baylis AL, Jensen JN, Kirschner RE, Shriberg LD: Motor Speech Deficits in 22q11.2 Deletion Syndrome. 2013, Orlando, FL, USA: Paper presented at the 12th International Congress on Cleft Lip/Palate and Related Craniofacial Anomalies
65.
Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR, Zumbo P, Nayir A, Bakkaloğlu A, Özen S, Sanjad S, Nelson-Williams C, Farhi A, Mane S, Lifton RP: Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009, 106: 19096-19101. 10.1073/pnas.0910672106.PubMedCentralPubMedCrossRef
66.
Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock DP, Evans JP, Grody WW, Hegde MR, Kalia S, Korf BR, Krantz I, McGuire AL, Miller DT, Murray MF, Nussbaum RL, Plon SE, Rehm HL, Jacob HJ: Exploring concordance and discordance for return of incidental findings from clinical sequencing. Genet Med. 2012, 14: 405-410. 10.1038/gim.2012.21.PubMedCentralPubMedCrossRef
67.
Goh V, Helbling D, Biank V, Jarzembowski J, Dimmock D: Next-generation sequencing facilitates the diagnosis in a child with twinkle mutations causing cholestatic liver failure. J Pediatr Gastroenterol Nutr. 2012, 54: 291-294. 10.1097/MPG.0b013e318227e53c.PubMedCrossRef
68.
Ng BG, Buckingham KJ, Raymond K, Kircher M, Turner EH, He M, Smith JD, Eroshkin A, Szybowska M, Losfeld ME, Chong JX, Kozenko M, Li C, Patterson MC, Gilbert RD, Nickerson DA, Shendure J, Bamshad MJ, Freeze HH, University of Washington Center for Mendelian Genomics: Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation. Am J Hum Genet. 2013, 92: 632-636. 10.1016/j.ajhg.2013.03.012.PubMedCentralPubMedCrossRef
69.
Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL, Basehore MJ, Broeckel U, Tomita-Mitchell A, Arca MJ, Casper JT, Margolis DA, Bick DP, Hessner MJ, Routes JM, Verbsky JW, Jacob HJ, Dimmock DP: Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med. 2011, 13: 255-262. 10.1097/GIM.0b013e3182088158.PubMedCrossRef
70.
Shriberg LD, Fourakis M, Hall S, Karlsson HK, Lohmeier HL, McSweeny J, Potter NL, Scheer-Cohen AR, Strand EA, Tilkens CM, Wilson DL: Extensions to the speech disorders classification system (SDCS). Clin Linguist Phonet. 2010, 24: 795-824. 10.3109/02699206.2010.503006.CrossRef
71.
Shriberg LD, Fourakis M, Hall S, Karlsson HK, Lohmeier HL, McSweeny J, Potter NL, Scheer-Cohen AR, Strand EA, Tilkens CM, Wilson DL: Perceptual and acoustic reliability estimates for the Speech Disorders Classification System (SDCS). Clin Linguist Phonet. 2010, 24: 825-846. 10.3109/02699206.2010.503007.CrossRef
72.
Kaufman AS, Kaufman NL: Kaufman Brief Intelligence Test, Second Edition (KBIT-2). 2004, London: Pearson
73.
Carrow-Woolfolk E: Oral and Written Language Scales (OWLS). 1995, Bloomington, MN: Pearson Assessment
74.
Shriberg LD, Kwiatkowski J: Developmental phonological disorders. I: A clinical profile. J Speech Hear Res. 1994, 37: 1100-1126.PubMedCrossRef
75.
Plagnol V, Curtis J, Epstein M, Mok KY, Stebbings E, Grigoriadou S, Wood NW, Hambleton S, Burns SO, Thrasher AJ, Kumararatne D, Doffinger R, Nejentsev S: A robust model for read count data in exome sequencing experiments and implications for copy number variant calling. Bioinformatics. 2012, 28: 2747-2754. 10.1093/bioinformatics/bts526.PubMedCentralPubMedCrossRef
76.
Dasen JS, De Camilli A, Wang B, Tucker PW, Jessell TM: Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell. 2008, 134: 304-316. 10.1016/j.cell.2008.06.019.PubMedCrossRef
77.
Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA: Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol. 2003, 460: 266-279. 10.1002/cne.10654.PubMedCrossRef
78.
Palmesino E, Rousso DL, Kao TJ, Klar A, Laufer E, Uemura O, Okamoto H, Novitch BG, Kania A: Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling. PLoS Biol. 2010, 8: e1000446-10.1371/journal.pbio.1000446.PubMedCentralPubMedCrossRef
79.
Wang B, Weidenfeld J, Lu MM, Maika S, Kuziel WA, Morrisey EE, Tucker PW: Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development. 2004, 131: 4477-4487. 10.1242/dev.01287.PubMedCrossRef
80.
Feng X, Ippolito GC, Tian L, Wiehagen K, Oh S, Sambandam A, Willen J, Bunte RM, Maika SD, Harriss JV, Caton AJ, Bhandoola A, Tucker PW, Hu H: Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development. Blood. 2010, 115: 510-518. 10.1182/blood-2009-07-232694.PubMedCentralPubMedCrossRef
81.
Shu W, Lu MM, Zhang Y, Tucker PW, Zhou D, Morrisey EE: Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development. 2007, 134: 1991-2000. 10.1242/dev.02846.PubMedCrossRef
82.
Vernes SC, MacDermot KD, Monaco AP, Fisher SE: Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia. Eur J Hum Genet. 2009, 17: 1354-1358. 10.1038/ejhg.2009.43.PubMedCentralPubMedCrossRef
83.
Hamdan FF, Daoud H, Rochefort D, Piton A, Gauthier J, Langlois M, Foomani G, Dobrzeniecka S, Krebs MO, Joober R, Lafrenière RG, Lacaille JC, Mottron L, Drapeau P, Beauchamp MH, Phillips MS, Fombonne E, Rouleau GA, Michaud JL: De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet. 2010, 87: 671-678. 10.1016/j.ajhg.2010.09.017.PubMedCentralPubMedCrossRef
84.
Palumbo O, D’Agruma L, Minenna AF, Palumbo P, Stallone R, Palladino T, Zelante L, Carella M: 3p14.1 de novo microdeletion involving the FOXP1 gene in an adult patient with autism, severe speech delay and deficit of motor coordination. Gene. 2013, 516: 107-113. 10.1016/j.gene.2012.12.073.PubMedCrossRef
85.
Abrahams BS, Tentler D, Perederiy JV, Oldham MC, Coppola G, Geschwind DH: Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc Natl Acad Sci U S A. 2007, 104: 17849-17854. 10.1073/pnas.0706128104.PubMedCentralPubMedCrossRef
86.
Al-Murrani A, Ashton F, Aftimos S, George AM, Love DR: Amino-terminal microdeletion within the CNTNAP2 gene associated with variable expressivity of speech delay. Case Rep Genet. 2012, 2012: 172408-PubMedCentralPubMed
87.
Devanathan V, Jakovcevski I, Santuccione A, Li S, Lee HJ, Peles E, Leshchyns’ka I, Sytnyk V, Schachner M: Cellular form of prion protein inhibits Reelin-mediated shedding of Caspr from the neuronal cell surface to potentiate Caspr-mediated inhibition of neurite outgrowth. J Neurosci. 2010, 30: 9292-9305. 10.1523/JNEUROSCI.5657-09.2010.PubMedCrossRef
88.
Rios JC, Melendez-Vasquez CV, Einheber S, Lustig M, Grumet M, Hemperly J, Peles E, Salzer JL: Contactin-associated protein (Caspr) and contactin form a complex that is targeted to the paranodal junctions during myelination. J Neurosci. 2000, 20: 8354-8364.PubMed
89.
Peles E, Salzer JL: Molecular domains of myelinated axons. Curr Opin Neurobiol. 2000, 10: 558-565. 10.1016/S0959-4388(00)00122-7.PubMedCrossRef
90.
Pillai AM, Garcia-Fresco GP, Sousa AD, Dupree JL, Philpot BD, Bhat MA: No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity. J Neurosci Res. 2007, 85: 2318-2331. 10.1002/jnr.21374.PubMedCentralPubMedCrossRef
91.
Gollan L, Salomon D, Salzer JL, Peles E: Caspr regulates the processing of contactin and inhibits its binding to neurofascin. J Cell Biol. 2003, 163: 1213-1218. 10.1083/jcb.200309147.PubMedCentralPubMedCrossRef
92.
Fogel BL, Perlman S: Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. Neurology. 2006, 67: 2083-2084. 10.1212/01.wnl.0000247661.19601.28.PubMedCrossRef
93.
Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, Delaunoy JP, Fritsch M, Arning L, Synofzik M, Schöls L, Sequeiros J, Goizet C, Marelli C, Le Ber I, Koht J, Gazulla J, De Bleecker J, Mukhtar M, Drouot N, Ali-Pacha L, Benhassine T, Chbicheb M, M’Zahem A, Hamri A, Chabrol B, Pouget J, Murphy R, Watanabe M, Coutinho P: Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain. 2009, 132: 2688-2698. 10.1093/brain/awp211.PubMedCrossRef
94.
Arning L, Epplen JT, Rahikkala E, Hendrich C, Ludolph AC, Sperfeld AD: The SETX missense variation spectrum as evaluated in patients with ALS4-like motor neuron diseases. Neurogenetics. 2013, 14: 53-61. 10.1007/s10048-012-0347-4.PubMedCrossRef
95.
Criscuolo C, Chessa L, Di Giandomenico S, Mancini P, Saccà F, Grieco GS, Piane M, Barbieri F, De Michele G, Banfi S, Pierelli F, Rizzuto N, Santorelli FM, Gallosti L, Filla A, Casali C: Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study. Neurology. 2006, 66: 1207-1210. 10.1212/01.wnl.0000208402.10512.4a.PubMedCrossRef
96.
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. Am J Hum Genet. 2004, 75: 1046-1058. 10.1086/426404.PubMedCentralPubMedCrossRef
97.
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: The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration. Hum Mol Genet. 2006, 15: 1659-1666. 10.1093/hmg/ddl089.PubMedCrossRef
98.
Peschansky VJ, Burbridge TJ, Volz AJ, Fiondella C, Wissner-Gross Z, Galaburda AM, Lo Turco JJ, Rosen JJ: The effect of variation in expression of the candidate dyslexia susceptibility gene homolog Kiaa0319 on neuronal migration and dendritic morphology in the rat. Cereb Cortex. 2010, 20: 884-897. 10.1093/cercor/bhp154.PubMedCentralPubMedCrossRef
99.
Poon MW, Tsang WH, Chan SO, Li HM, Ng HK, Waye MM: Dyslexia-associated Kiaa0319-like protein interacts with axon guidance receptor Nogo receptor 1. Cell Mol Neurobiol. 2011, 31: 27-35. 10.1007/s10571-010-9549-1.PubMedCrossRef
100.
Streets AJ, Newby LJ, O’Hare MJ, Bukanov NO, Ibraghimov-Beskrovnaya O, Ong AC: Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell-cell adhesion. Am Soc Nephrol. 2003, 14: 1804-1815. 10.1097/01.ASN.0000076075.49819.9B.CrossRef
101.
Szalkowski CE, Fiondella CG, Galaburda AM, Rosen GD, Loturco JJ, Fitch RH: Neocortical disruption and behavioral impairments in rats following in utero RNAi of candidate dyslexia risk gene Kiaa0319. Int J Dev Neurosci. 2012, 30: 293-302. 10.1016/j.ijdevneu.2012.01.009.PubMedCentralPubMedCrossRef
102.
Dennis MY, Paracchini S, Scerri TS, Prokunina-Olsson L, Knight JC, Wade-Martins R, Coggill P, Beck S, Green ED, Monaco AP: A common variant associated with dyslexia reduces expression of the KIAA0319 gene. PLoS Genet. 2009, 5: e1000436-10.1371/journal.pgen.1000436.PubMedCentralPubMedCrossRef
103.
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. J Neurodev Disord. 2009, 1: 264-282. 10.1007/s11689-009-9031-x.PubMedCentralPubMedCrossRef
104.
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. Am J Hum Genet. 2005, 76: 581-591. 10.1086/429131.PubMedCentralPubMedCrossRef
105.
Zou L, Chen W, Shao S, Sun Z, Zhong R, Shi J, Miao X, Song R: Genetic variant in KIAA0319, but not in DYX1C1, is associated with risk of dyslexia: an integrated meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2012, 159B: 970-976. 10.1002/ajmg.b.32102.PubMedCrossRef
106.
Snowling M, Bishop DV, Stothard SE: Is preschool language impairment a risk factor for dyslexia in adolescence?. J Child Psychol Psychiatry. 2000, 41: 587-600. 10.1111/1469-7610.00651.PubMedCrossRef
107.
Vallipuram J, Grenville J, Crawford DA: The E646D-ATP13A4 mutation associated with autism reveals a defect in calcium regulation. Cell Mol Neurobiol. 2010, 30: 233-246. 10.1007/s10571-009-9445-8.PubMedCrossRef
108.
Kwasnicka-Crawford DA, Carson AR, Roberts W, Summers AM, Rehnström K, Järvelä I, Scherer SW: Characterization of a novel cation transporter ATPase gene (ATP13A4) interrupted by 3q25–q29 inversion in an individual with language delay. Genomics. 2005, 86: 182-194. 10.1016/j.ygeno.2005.04.002.PubMedCrossRef
109.
Taylor LJ, Maybery MT, Grayndler L, Whitehouse AJ: Evidence for distinct cognitive profiles in autism spectrum disorders and specific language impairment. J Autism Dev Disord. in press. doi:10.1007/s10803-013-1847-2
110.
Leblond CS, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G, Konyukh M, Chaste P, Ey E, Rastam M, Anckarsäter H, Nygren G, Gillberg IC, Melke J, Toro R, Regnault B, Fauchereau F, Mercati O, Lemière N, Skuse D, Poot M, Holt R, Monaco AP, Järvelä I, Kantojärvi K, Vanhala R, Curran S, Collier DA, Bolton P, Chiocchetti A: Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 2012, 8: e1002521-10.1371/journal.pgen.1002521.PubMedCentralPubMedCrossRef
111.
Ruzzo EK, Pappas AL, Goldstein DB: Modifier genetics in neuropsychiatric disease: challenges and opportunities. Genome Biol. 2012, 13: 150-10.1186/gb-2012-13-3-150.PubMedCentralPubMedCrossRef
112.
Lander E, Kruglyak L: Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995, 11: 241-247. 10.1038/ng1195-241.PubMedCrossRef
Metadata
Title
Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech
Authors
Elizabeth A Worthey
Gordana Raca
Jennifer J Laffin
Brandon M Wilk
Jeremy M Harris
Kathy J Jakielski
David P Dimmock
Edythe A Strand
Lawrence D Shriberg
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2013
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/1866-1955-5-29

Other articles of this Issue 1/2013

Journal of Neurodevelopmental Disorders 1/2013 Go to the issue

Research

The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome

Research

A pilot open-label trial of minocycline in patients with autism and regressive features

New method

A quantitative homogeneous assay for fragile X mental retardation 1 protein

Research

Dementia in Down’s syndrome: an MRI comparison with Alzheimer’s disease in the general population

Research

Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

Research

Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study