Localisation of a gene implicated in a severe speech and language disorder

  title={Localisation of a gene implicated in a severe speech and language disorder},
  author={Simon E. Fisher and Faraneh Vargha-Khadem and Kate E. Watkins and Anthony P. Monaco and Marcus E Pembrey},
  journal={Nature Genetics},
Between 2 and 5% of children who are otherwise unimpaired have significant difficulties in acquiring expressive and/or receptive language, despite adequate intelligence and opportunity1,2. While twin studies indicate a significant role for genetic factors in developmental disorders of speech and language1, the majority of families segregating such disorders show complex patterns of inheritance, and are thus not amenable for conventional linkage analysis2. A rare exception is the KE family, a… 

A forkhead-domain gene is mutated in a severe speech and language disorder

It is suggested that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is involved in the developmental process that culminates in speech and language.

The Genetic Basis of a Severe Speech and Language Disorder

Mutation screening of FOXP2 in the KE family revealed a point mutation in all affected individuals, which leads to alteration of a key residue in the DNA-binding domain, and is predicted to disrupt the func­tion of the protein.

Genetics of speech and language disorders.

  • C. KangD. Drayna
  • Biology, Psychology
    Annual review of genomics and human genetics
  • 2011
The discovery of mutations in the FOXP2 gene led to a new avenue of investigation into the substrates and mechanisms that underlie human speech development, and linkage studies have identified several loci, and candidate gene association studies are making progress in identifying causal variants at these loci.

Towards the elucidation of the genetic and brain bases of developmental speech and language disorders.

The case for a causal association is further strengthened by the finding of a translocation break in the same gene in another unrelated individual who has a very similar speech and language disorder (Lai et al ., 2001).

Genetic Pathways Implicated in Speech and Language

Although FOXP2 was initially uncovered in humans, model systems have been invaluable in progressing understanding of the function of this gene and its associated pathways in language-related areas of the brain and ongoing work in animal models promises to yield new insights into the genetic and neural mechanisms underlying human speech and language.

Support for linkage of autism and specific language impairment to 7q3 from two chromosome rearrangements involving band 7q31.

Two individuals are presented with different, apparently balanced chromosome rearrangements involving a breakpoint at 7q31, and the findings may be of interest and relevance to the genetic aetiology of autism, and helpful in the search for susceptibility loci for SDDSL and autism.

HUMAN GENETICS ’99 Functional and Structural Brain Abnormalities Associated with a Genetic Disorder of Speech and Language

The number of children diagnosed with developmental disorders, such as dyslexia, autism, specific language impairment, and attention deficit disorder, is increasing, as these disorders become better

Genetic studies on speech and language disorders

Although studies have increased understanding of the genetic causes of speech and language disorders, these genes can only explain a small fraction of all disorders in patients.

Association of specific language impairment (SLI) to the region of 7q31.

Strong association was found to a marker within the CFTR gene and another marker on 7q31, D7S3052, both adjacent toFOXP2, suggesting that genetic factors for regulation of common language impairment reside in the vicinity of FOXP2.

Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.

Investigation of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia and the discovery of the first nonsense mutation in FoxP2 opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene.



Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder.

Investigations of the same KE family indicate that the inherited disorder has a broad phenotype which transcends impaired generation of syntactical rules and includes a striking articulatory impairment as well as defects in intellectual, linguistic, and orofacial praxic functions generally.


There is good evidence that genetic factors play a role in the aetiology of speech and language impairment; twin data may help to arrive at a clearer conception of the phenotype as well as quantifying the extent of the genetic contribution.

An extended Family with a Dominantly Inherited Speech Disorder

A three‐generation family is described in which 16 members have a severe developmental verbal dyspraxia. Inheritance is autosomal dominant, with full penetrance. Intelligence and hearing are normal.

A comprehensive genetic map of the human genome based on 5,264 microsatellites

The last version of the Généthon human linkage map is reported, which consists of 5,264 short tandem repeat polymorphisms with a mean heterozygosity of 70%.

A Gene Map of the Human Genome

The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease.

A physical map of human chromosome 7: an integrated YAC contig map with average STS spacing of 79 kb.

The physical map of human chromosome 7, a approximately 170-Mb segment of DNA that corresponds to an estimated 5% of the human genome, exceeds the goal of 100-kb average STS spacing and should provide an excellent framework for systematic sequencing of the chromosome.

Periventricular Leukomalacia: Ultrasonic and Neuropathological Correlations

Ultrasound scans of a preterm neonate at seven weeks of age showed periventricular echo‐ free cavities, but these were no longer visible at 15 weeks, three weeks before the infant died, demonstrating that transient echo‐free cavities represent foci of cystic necrosis, which are subject to secondary collapse.

Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.

Algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis are explored.

Chromosome–specific microsatellite sets for fluorescence–based, semi–automated genome mapping

To facilitate large–scale genetic mapping of the human genome, we have developed chromosome–specific sets of microsatellite marker loci suitable for use with a fluorescence–based automated DNA