Speech/Language Disorders Database

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Gene / phenotype associations for CFTR

  • Click column headers to sort. Click to expand any row to see more details about the particular assertion of an association between variants of CFTR and a particular phenotypic variable.
  • Click the Pubmed IDs in the last column to link out to the primary research article. Click the links in the last column to download the full Genotype-Phenotype record as JSON or XML formatted text.
Entrez Id Symbol Location Disorder Brief Phenotype Reference Year Download
1080 CFTR 7q31.2 SLI Susceptibility to Specific Language Impairment O'Brien et al 2003 JSON | XML

Additional Phenotype Details: 
Specific Language Impairment may be diagnosed based on an expressive and/or receptive language score less than a certain number of SDs (e.g. 1.5) below the mean for the individual's age on a test such as the Clinical Evaluation of Language Fundamentals (CELF). Usually, a Performance Intelligence Quotient (PIQ) of at least 70 or 80 on the age-appropriate Weschler test is also a criterion. See Tomblin et al 1996 for a specific system for diagnosing SLI.


Semel EM, Wiig EH, Secord W (1992) Clinical evaluation of language fundamentals—revised. Phychological Corporation, San Antonio.

Tomblin JB, Records NL, Zhang X (1996) A system for the diagnosis of specific language impairment in kindergarten children. J Speech Hear Res 39:1284–1294.

Wechsler D. 1991. Wechsler intelligence scale for children- third edition (WISC-III). San Antonio: The Psychological Corporation.

Basic Study Type:  Association and linkage studies

Study Cohort: 
Summary: 1608 individuals, 604 families

All subjects were genotyped. 96 probands were also "directly sequenced for the mutation in exon 14 of FOXP2."


"The participants of the present study consisted of probands identified in a population-based study of children with and without language impairment who are being followed during their school years. The probands were identified when they were in kindergarten from a sample of children enrolled in schools in Iowa and Illinois. All 7,218 children from the chosen communities were given a language-screening test. Those who failed and one-third of those who passed were sampled for a more complete language, speech, hearing, and IQ assessment. By use of this information, children were diagnosed with respect to their language status, in accordance with a system described by Tomblin et al. (1996). The results of the screening and diagnosis were published in a study that found a 7.4% incidence of SLI in that group (Tomblin et al. 1997). The parents of 1,744 participants who received the diagnostic evaluations were asked to participate in a registry for future research. From this registry, 604 children were sampled to participate in a longitudinal study. This sample consisted of all children who were language impaired and for whom assent was obtained, as well as a random sample of those children with assent who were developing typically. Phenotypic measures were obtained in second grade for all these children (table 1). Information was also collected on the language phenotype of the siblings of the probands through assessment with one of three language batteries, depending upon the siblings’ ages (table 2). High between-battery correlations had been obtained with these tests, indicating that they were testing the same traits in siblings and probands. Performance IQ (PIQ) was assessed by the performance battery of Wechsler Intelligence Scale for Children-Third Edition (Wechsler 1991). Only children with a PIQ >70 were included in the statistical analysis."

Genotyping Methods: 
"The samples were genotyped for microsatellite repeats in chromosome 7 by amplification of the region by PCR. The PCR product was run on denaturing 6% polyacrylamide gel, and bands were visualized via silver staining. All samples were genotyped for a tetranucleotide repeat (GATT) in the CFTR gene, a marker chosen for ease in genotyping on sequencing gels (Gasparini et al. 1991) as well as its location in the region of critical interest, 3 Mb distal to FOXP2 on 7q31. Next, two tetranucleotide repeat CHLC markers in 7q31, D7S1817 and D7S3052, located 5 Mb proximal to FOXP2, were used to genotype all samples using standard CHLC PCR conditions (Murray et al. 1994). Using a GATA repeat in intron 2 of FOXP2 with primers designed by Wassink et al. (2002), all samples—including those from affected individuals, their family members, and controls—were genotyped, for a total of 1,608 genotyped individuals. By use of the published sequence of FOXP2 available on the Human Genome Gateway Browser and Sequencher 4.1, six additional tetranucleotide repeats were found within the intronic regions of FOXP2, as described by Lai et al. (2001). Primers were designed to amplify these microsatellite repeats, and genotypes were generated for a subset of samples. These genotypes were used to calculate the degree of linkage disequilibrium between the seven markers in FOXP2 using the GOLD program (Abecasis and Cookson 2000). Two markers, both TTTA repeats within the intronic regions between exons 1 and 2 and exons 3a and 3b of FOXP2 (Lai et al. 2001; Bruce and Margolis 2002), were not in linkage disequilibrium with the GATA repeat and were used to genotype samples from families with siblings. A total of 781 samples were genotyped for all three markers. These genotypes were analyzed again to confirm that the additional markers were not in linkage disequilibrium with the GATA repeat and therefore would provide additional information to test for association. Primers and PCR conditions are available upon request."

Analysis Methods: 
The authors performed sib-pair linkage with both the discrete phenotype and the continuous test scores.

For the association analysis, "affected family–based controls (AFBAC) analysis and the extended transmission/disequilibrium test (ETDT) for multiple alleles were used with the discrete language phenotype, and the quantitative transmission/disequilibrium test (QTDT) was used with the continuous language scores."

Other Details: Diagnostic criterion:

Composite language score of 1.14 SDs below the mean for second grade.

Tests for probands:

PPVT-R, CREVET, CELF-III (Sentence structures, concepts and directions; listening to paragraphs; word structure, recalling sentences), and narrative generation (total clauses)

Tests for siblings:

Ages 4-6:
TOLD-2:P (picture vocabulary, oral vocabulary, grammatic understanding, sentence imitation, grammatic completion)
Ages 7-8:
PPVT-R and CELF-III (sentence structures, concepts and directions, word structures, recalling sentences, listening to paragraphs)
Ages 9-14:
PPVT-R and CELF-III (formulated sentences, concepts and directions, recalling sentences, listening to paragraphs)

Associated Markers:
D7S3052  (P = 0.003; 0.0096)  - P-values for Extended Transmission / Disequilibrium Test (ETDT) and Affected Family-based Controls (AFBAC) analyses, respectively
CFTR GATT repeat  (P = 0.0014; 0.0001)  - P-values for Extended Transmission / Disequilibrium Test (ETDT) and Affected Family-based Controls (AFBAC) analyses, respectively


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