The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
A Functional Genetic Link between Distinct Developmental Language Disorders
Open accessAbstract
BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Several groups have demonstrated that this is indeed the case with respect to CNTNAP2 [60, 61, 63], as the same allele that increases risk for language delay in ASD, increases risk for specific language impairment (SLI) and modifies language ability in the general population.”
From Genetics of autism spectrum disorders (2011) · cites this paper as [61]
In the citing paper
“Two common polymorphisms in a relatively circumscribed area of CNTNAP2 have been shown to modulate language function in ASD and other conditions [59–61].”
From Genetics of autism spectrum disorders (2011) · cites this paper as [61]
In the citing paper
“Common variants in CNTNAP2 have also been associated with ASD (49–51) and specific-language impairment (52).”
From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [52]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Merlin—rapid analysis of dense genetic maps using sparse gene flow trees
Abecasis, G. R., Cherny, S. S., Cookson, W., & Cardon, L. R. (2001) · Nature Genetics · doi:10.1038/ng786 · Cited by 3,323
Prevalence of Specific Language Impairment in Kindergarten Children
Tomblin, J. B., Records, N. L., Buckwalter, P., Zhang, X., Smith, E., & O’Brien, M. (1997) · Journal of Speech, Language, and Hearing Research · doi:10.1044/jslhr.4006.1245 · Cited by 2,288
A forkhead-domain gene is mutated in a severe speech and language disorder
Lai, C. S. L., Fisher, S. E., Hurst, J. A., Vargha‐Khadem, F., & Monaco, A. P. (2001) · Nature · doi:10.1038/35097076 · Cited by 2,053
Self-citationThe UCSC Genome Browser Database
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg129 · Cited by 1,890
A General Test of Association for Quantitative Traits in Nuclear Families
Abecasis, G. R., Cardon, L. R., & Cookson, W. O. C. (2000) · The American Journal of Human Genetics · doi:10.1086/302698 · Cited by 1,126
Cawley, S., Bekiranov, S., Ng, H. H., Kapranov, P., Sekinger, E. A., Kampa, D., Piccolboni, A., Sementchenko, V., Cheng, J., Williams, A. J., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00127-8 · Cited by 1,095
Time to give up on a single explanation for autism
Happé, F., Ronald, A., & Plomin, R. (2006) · Nature Neuroscience · doi:10.1038/nn1770 · Cited by 987
Nonword repetition and word learning: The nature of the relationship
Gathercole, S. E. (2006) · Applied Psycholinguistics · doi:10.1017/s0142716406060383 · Cited by 959
The children's test of nonword repetition: A test of phonological working memory
Gathercole, S. E., Willis, C., Baddeley, A., & Emslie, H. C. (1994) · Memory · doi:10.1080/09658219408258940 · Cited by 898
Cited by
Sorted by citations
The myth of language universals: Language diversity and its importance for cognitive science
Evans, N., & Levinson, S. C. (2009) · Behavioral and Brain Sciences · doi:10.1017/s0140525x0999094x · Cited by 2,745
A high-coverage genome sequence from an archaic denisovan individual
Meyer, M., Kircher, M., Gansauge, M.-T., Li, H., Racimo, F., Mallick, S., Schraiber, J. G., Jay, F., Prüfer, K., de Filippo, C., et al. (2012) · Science · doi:10.1126/science.1224344 · Cited by 1,967
Evolution of the neocortex: a perspective from developmental biology
Rakic, P. (2009) · Nature reviews. Neuroscience · doi:10.1038/nrn2719 · Cited by 1,565
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203
Self-citationInterneuron dysfunction in psychiatric disorders
Marín, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3155 · Cited by 1,190
Metadata
- Authors
- Vernes, S. C., Newbury, D. F., Abrahams, B. S., Winchester, L., Nicod, J., Groszer, M., Alarcón, M., Oliver, P. L., Davies, K. E., Geschwind, D. H., Monaco, A. P., & Fisher, S. E.
- Affiliations
- Centre for Human Genetics (GB)
- University of California, Los Angeles (US)
- University of Oxford (GB)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-11-27
- Volume
- 359
- Issue
- 22
- Pages
- 2337-2345
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2756409
- OpenAlex
- W2152704739
- Cited by
- 676
- References
- 51
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 18 · 2023: 22 · 2022: 9 · 2021: 25 · 2020: 21 · 2019: 25 · 2018: 36 · 2017: 34 · 2016: 36 · 2015: 40 · 2014: 56 · 2013: 59 · 2012: 80
- FWCI
- 111.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Autism Speaks (AS1309)
- Wellcome Trust (080971)
- National Institute of Mental Health (MH75028-R21, R21MH075028, R01MH060233, MH081754-R01, R01MH081754, MH60233-R37, R56MH060233, R37MH060233)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD055784-P50, P50HD055784)
- Topics
- Social Sciences › Psychology › Developmental and Educational Psychology › Language Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Developmental and Educational Psychology › Reading and Literacy Development
- Keywords
- FOXP2, CNTNAP2, neurexin, specific language impairment, transcriptional regulation, single nucleotide polymorphisms, genetic linkage, chromatin immunoprecipitation, speech and language disorders
- MeSH terms
- Child, Female, Gene Expression Regulation, Genetic Markers, Haplotypes, Humans, Language Development Disorders, Male, Membrane Proteins, Nerve Tissue Proteins, Phenotype, Down-Regulation, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Chromatin Immunoprecipitation, Forkhead Transcription Factors, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
