KE family

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The KE family is a medical name designated for a British family, about half of whom exhibit a severe speech disorder called developmental verbal dyspraxia. [1] It is the first family with speech disorder to be investigated using genetic analyses, by which the speech impairment is discovered to be due to genetic mutation, and from which the gene FOXP2 , often dubbed the "language gene", was discovered. Their condition is also the first human speech and language disorder known to exhibit strict Mendelian inheritance. [2]

Contents

Brought to medical attention from their school children in the late 1980s, the case of KE family was taken up at the UCL Institute of Child Health in London in 1990. Initial report suggested that the family was affected by a genetic disorder. Canadian linguist Myrna Gopnik suggested that the disorder was characterized primarily by grammatical deficiency, supporting the controversial notion of a "grammar gene". Geneticists at the University of Oxford determined that the condition was indeed genetic, with complex physical and physiological effects, and in 1998, they identified the actual gene, eventually named FOXP2 . Contrary to the grammar gene notion, FOXP2 does not control any specific grammar or language output. This discovery directly led to a broader knowledge on human evolution as the gene is directly implicated with the origin of language. [3]

Two family members, a boy and a girl, were featured in the National Geographic documentary film Human Ape . [4]

Background and identity

The individual identity of the KE family are kept confidential. The family children attended Elizabeth Augur's special educational needs unit at the Lionel Primary School in Brentford, West London. Towards the end of 1980s, seven children of the family attended there. [5] Augur began to learn that the family had a speech disorder for three generations. Of the 30 members, half of them had severe disability, some are affected mildly, and few are unaffected. [6] Their faces show rigidity at the lower half, and most cannot complete pronouncing a word. Many of them have severe stuttering and with limited vocabulary. In particular, they have difficulty with consonants, and omit them, such as "boon" for "spoon", "able" for "table", and "bu" for "blue". Linguistic deficiency is also noted in written language both in reading and writing. They are characterized by lower nonverbal IQ. [7]

Ethnicity

When the first study on KE family was published in 1990, the exact identity of the family was withheld and simply indicated as living in West London. [8] The first genetic study reported in 1995 revealed that they were 30 members of four generations, with the designation "KE family." [7] In 2009, American psychologist Elena L. Grigorenko of Yale University wrote a review paper on the genetics of developmental disorders in which she specifically described a case of speech disorder in a "three-generation pedigree of Pakistani origin from the United Kingdom (referred to as KE)." [9] When a team of researchers from Germany, led by Arndt Wilcke of the Leipzig University, reported in 2011 the effects of FOXP2 mutation in the brain, they mentioned the family as "a large Pakistani family with severe speech and language disorder." [10]

The British-Pakistani description for the family became widely used. [11] [12] [13] [14] However, British geneticist and neuroscientist Simon E. Fisher at the Max Planck Institute for Psycholinguistics pointed out the error in Wilcke's paper to which the German team published a corrigendum that KE family were not of Pakistani descent, but "a large English Caucasian family." [15]

Research investigations

Augur convinced the family to undergo medical examinations and approached geneticist Michael Baraitser at the Institute of Child Health. With colleagues Marcus Pembrey and Jane Hurst at the Hospital for Sick Children (Great Ormond Street Hospital), they started taking blood samples for analyses in 1987. Their first report in 1990 shows that 16 family members were affected by severe abnormality, characterised by difficulty to speak effectively, understand complex sentences, unable to learn sign language, and that the condition was genetically inherited (autosomal dominant). Their conclusion runs:

Of the 16 affected children, none had significant feeding difficulties as infants and there were few neonatal problems. Hearing and intelligence of all affected members were within the normal range. The speech problem in this family has been classified as developmental verbal dyspraxia. [8]

Upon the news, BBC was preparing a documentary of the case in the scientific serial Antenna. By this time, a Canadian linguist from McGill University, Myrna Gopnik, was visiting her son in Oxford, and delivered an invited lecture at the university, where she noticed the flyer for the BBC programme. She contacted the medical geneticists, interviewed KE family members, and returned to Montreal, Quebec. She was convinced that the genetic defect was largely centred on grammatical ability, and wrote letters to Nature in 1990. [16] [17] Her reports promulgated a notion of "grammar gene" and a controversial concept of grammar-specific disorder. [18] [19]

Discovery of FOXP2 gene

Neuroscientist and language expert at the Institute of Child Health Faraneh Vargha-Khadem began to investigate teaming up with University of Oxford and University of Reading linguists. In 1995 they found, contrary to Gopnik's hypothesis, from comparison of 13 affected and 8 control individuals that the genetic disorder was a complex impairment of not only linguistic ability, but also intellectual and anatomical features, thereby disproving the "grammar gene" notion. [7] Using positron emission tomography (PET) and magnetic resonance imaging (MRI), they found that some brain regions were underactive (compared to baseline levels) in the KE family members and that some were overactive, when compared to people without the condition. The underactive regions included motor neurons that control face and mouth regions. The areas that were overactive includes Broca's area, the speech centre. [20] With Oxford geneticists Kate Watkins, Simon Fisher and Anthony Monaco, they identified the exact location of the gene on the long arm of chromosome 7 (7q31) in 1998. [21] The chromosomal region (locus) was named SPCH1 (for speech-and-language-disorder-1), and it contains 70 genes. [22] Using the known gene location of speech disorder from a boy, designated CS, of unrelated family, they discovered in 2001 that the main gene responsible for speech impairment in both KE family and CS was FOXP2. [23] Mutations in the genes result in speech and language problems. [24] [25] [26]

See also

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References

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  3. ↑ Preuss TM (June 2012). "Human brain evolution: from gene discovery to phenotype discovery". Proceedings of the National Academy of Sciences of the United States of America. 109 (Supplement 1): 10709–10716. Bibcode:2012PNAS..10910709P. doi: 10.1073/pnas.1201894109 . PMC   3386880 . PMID   22723367.
  4. ↑ "Human Ape". natgeotv.com. NGC Europe Limited. Archived from the original on July 7, 2010. Retrieved 31 October 2014.
  5. ↑ Taylor J (2009). Not a Chimp: The Hunt to Find the Genes that Make Us Human. Oxford: Oxford University Press. ISBN   978-0-1916-1358-6.
  6. ↑ Watkins KE, Gadian DG, Vargha-Khadem F (November 1999). "Functional and structural brain abnormalities associated with a genetic disorder of speech and language". American Journal of Human Genetics. 65 (5): 1215–1221. doi:10.1086/302631. PMC   1288272 . PMID   10521285.
  7. 1 2 3 Vargha-Khadem F, Watkins K, Alcock K, Fletcher P, Passingham R (January 1995). "Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder". Proceedings of the National Academy of Sciences of the United States of America. 92 (3): 930–933. Bibcode:1995PNAS...92..930V. doi: 10.1073/pnas.92.3.930 . PMC   42734 . PMID   7846081.
  8. 1 2 Hurst JA, Baraitser M, Auger E, Graham F, Norell S (April 1990). "An extended family with a dominantly inherited speech disorder". Developmental Medicine and Child Neurology. 32 (4): 352–355. doi:10.1111/j.1469-8749.1990.tb16948.x. PMID   2332125. S2CID   2654363.
  9. ↑ Grigorenko EL (April 2009). "At the height of fashion: what genetics can teach us about neurodevelopmental disabilities". Current Opinion in Neurology. 22 (2): 126–130. doi:10.1097/WCO.0b013e3283292414. PMC   2891771 . PMID   19532035.
  10. ↑ Wilcke A, Ligges C, Burkhardt J, Alexander M, Wolf C, Quente E, et al. (February 2012) [2011]. "Imaging genetics of FOXP2 in dyslexia". European Journal of Human Genetics. 20 (2): 224–229. doi:10.1038/ejhg.2011.160. PMC   3260915 . PMID   21897444.
  11. ↑ Pennisi A, Falzone A (2016). "Genetic Fundamentals". Darwinian Biolinguistics: Theory and History of a Naturalistic Philosophy of Language and Pragmatics. Perspectives in Pragmatics, Philosophy & Psychology. Vol. 12. Springer. p. 102. doi:10.1007/978-3-319-47688-9_8. ISBN   978-3-319-47688-9.
  12. ↑ Lyons M, Harrison N, Brewer G, Robinson S, Sanders R (2014). Biological Psychology. Learning Matters. p. 137. ISBN   978-0-85725-695-9.
  13. ↑ "Origins of FOXP2 | Language as a biological adaption". blogs.ntu.edu.sg. Retrieved 2022-10-08.
  14. ↑ "The "speech gene" FOXP2 turned out to be a high-level regulator. Language gene Gene responsible for speech". historyancient.ru. Retrieved 2022-10-08.
  15. ↑ Wilcke A, Jana Burkhardt CL, Alexander M, Wolf C, Quente E, Ahnert P, et al. (2012). "Erratum: Imaging genetics of FOXP2 in dyslexia". European Journal of Human Genetics. 20 (6): 714. doi:10.1038/ejhg.2012.31. ISSN   1018-4813. PMC   3355268 .
  16. ↑ Gopnik M (September 1990). "Genetic basis of grammar defect". Nature. 347 (6288): 26. Bibcode:1990Natur.347...26G. doi: 10.1038/347026a0 . PMID   2395458.
  17. ↑ Gopnik M (April 1990). "Feature-blind grammar and dysphagia". Nature. 344 (6268): 715. Bibcode:1990Natur.344..715G. doi: 10.1038/344715a0 . PMID   2330028. S2CID   4360334.
  18. ↑ Cowie F (1999). What's Within?: Nativism Reconsidered. New York, US: Oxford University Press. pp. 290–291. ISBN   978-0-1951-5978-3.
  19. ↑ Jenkins L (2000). Biolinguistics: Exploring the Biology of Language (Revised ed.). Cambridge, UK: Cambridge University Press. pp. 98–99. ISBN   978-0-5210-0391-9.
  20. ↑ Vargha-Khadem F, Watkins KE, Price CJ, Ashburner J, Alcock KJ, Connelly A, et al. (October 1998). "Neural basis of an inherited speech and language disorder". Proceedings of the National Academy of Sciences of the United States of America. 95 (21): 12695–12700. Bibcode:1998PNAS...9512695V. doi: 10.1073/pnas.95.21.12695 . PMC   22893 . PMID   9770548.
  21. ↑ Fisher SE, Vargha-Khadem F, Watkins KE, Monaco AP, Pembrey ME (February 1998). "Localisation of a gene implicated in a severe speech and language disorder". Nature Genetics. 18 (2): 168–170. doi:10.1038/ng0298-168. hdl: 11858/00-001M-0000-0012-CBD9-5 . PMID   9462748. S2CID   3190318.
  22. ↑ "Genes that are essential for speech". The Brain from Top to Bottom. Retrieved 31 October 2014.
  23. ↑ Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP (October 2001). "A forkhead-domain gene is mutated in a severe speech and language disorder". Nature. 413 (6855): 519–523. Bibcode:2001Natur.413..519L. doi:10.1038/35097076. hdl: 11858/00-001M-0000-0012-CB9C-F . PMID   11586359. S2CID   4421562.
  24. ↑ Braten S, ed. (2007). On being moved : from mirror neurons to empathy. Amsterdam [u.a.]: John Benjamins Publication. ISBN   978-9-027252043.
  25. ↑ Vargha-Khadem F, Liegeois F (2007). "From speech to gene: The KE family and the FOXP2". In Braten S (ed.). On Being Moved : From Mirror Neurons to Empathy. Amsterdam: John Benjamins Publication. p. 11. ISBN   978-9-027252043. OCLC   643718628.
  26. ↑ Fisher SE, Scharff C (April 2009). "FOXP2 as a molecular window into speech and language". Trends in Genetics. 25 (4): 166–177. doi:10.1016/j.tig.2009.03.002. hdl: 11858/00-001M-0000-0012-CA31-7 . PMID   19304338.
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