Deciphering the genetic basis of speech and language disorders.

@article{Fisher2003DecipheringTG,
  title={Deciphering the genetic basis of speech and language disorders.},
  author={Simon E. Fisher and Cecilia S. L. Lai and Anthony P. Monaco},
  journal={Annual review of neuroscience},
  year={2003},
  volume={26},
  pages={
          57-80
        }
}
A significant number of individuals have unexplained difficulties with acquiring normal speech and language, despite adequate intelligence and environmental stimulation. Although developmental disorders of speech and language are heritable, the genetic basis is likely to involve several, possibly many, different risk factors. Investigations of a unique three-generation family showing monogenic inheritance of speech and language deficits led to the isolation of the first such gene on chromosome… 

Figures from this paper

Dissection of molecular mechanisms underlying speech and language disorders

  • S. Fisher
  • Biology, Psychology
    Applied Psycholinguistics
  • 2005
Consideration of findings from multiple levels of analysis demonstrates that FOXP2 cannot be characterized as “the gene for speech,” but rather as one critical piece of a complex puzzle, indicating that anyone expecting simple explanations of etiology or evolution should be prepared for some intriguing surprises.

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.

Unravelling neurogenetic networks implicated in developmental language disorders.

Although mutations of FOXP2 itself are rare, the downstream networks which it regulates in the brain appear to be broadly implicated in typical forms of language impairment, through ongoing identification of regulated targets and interacting co-factors.

A Window on the Genetics of Human Speech: The FOXP2 Gene

Molecular genetic studies revealed a mutation in the FOXP2 gene as possible basis of SLI in patients with special language impairment, indicating a common, ancestral population 3-400,000 years ago.

Molecular windows into speech and language disorders

  • S. Fisher
  • Biology
    International Journal of Developmental Neuroscience
  • 2006
How a recent paradigm shift has occurred and ways of bridging the gaps between molecules, neurons and the brain will provide a new understanding of the aetiology of speech and language impairments are demonstrated.

The genetic bases of speech sound disorders: evidence from spoken and written language.

It is hypothesized that underlying common cognitive traits, or endophenotypes, are responsible for shared genetic influences of spoken and written language and that many genes contribute to SSD.

Functional genetic analysis of mutations implicated in a human speech and language disorder.

It is hypothesize that expression of alternative isoforms of FOXP2 may provide mechanisms for post-translational regulation of transcription factor function, and explore the properties of different isoforms, resulting from alternative splicing in human brain.

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.

Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech

This work investigated the genetic etiology of CAS in two large multigenerational families with familial CAS and results are consistent with a heterogeneous CAS etiology, as is expected in many neurogenic disorders.
...

References

SHOWING 1-10 OF 76 REFERENCES

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.

Behavioural analysis of an inherited speech and language disorder: comparison with acquired aphasia.

Investigations of the KE family, half the members of which are affected by a severe disorder of speech and language, are reported, suggesting that, in the affected family members, the verbal and non-verbal deficits arise from a common impairment in the ability to sequence movement or in procedural learning.

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.

MRI analysis of an inherited speech and language disorder: structural brain abnormalities.

The results provide further evidence of a relationship between the abnormal development of this nucleus and the impairments in oromotor control and articulation reported in the KE family.

Neural basis of an inherited speech and language disorder.

The genetic mutation or deletion in this region has resulted in the abnormal development of several brain areas that appear to be critical for both orofacial movements and sequential articulation, leading to marked disruption of speech and expressive language.

A genomewide scan identifies two novel loci involved in specific language impairment.

Both the clinical and epidemiological samples showed independent evidence of linkage on both chromosome 16q and chromosome 19q, indicating that these may represent universally important loci in SLI and, thus, general risk factors for language impairment.

Molecular evolution of FOXP2, a gene involved in speech and language

It is shown that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution.

A major susceptibility locus for specific language impairment is located on 13q21.

Five pedigrees of Celtic ancestry are collected, and genomewide categorical linkage analysis is conducted, using model-based LOD score techniques, underscore the utility of traditional LOD-score-based methods in finding genes for complex diseases, specifically, SLI.

FOXP2 is not a major susceptibility gene for autism or specific language impairment.

It is concluded that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.

FOXP 2 Is Not a Major Susceptibility Gene for Autism or Specific Language Impairment

It is concluded that coding-region variants in FOXP2 do not underlie the AUTS1 linkage and that the gene is unlikely to play a role in autism or more common forms of language impairment.
...