KE family

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]

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. 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]

Medical investigations

KE family children attended Elizabeth Augur's special educational needs unit at Brentford primary school in 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, about half suffer from severe deficiency, 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]

Augur convinced the family to undergo medical studies and approached geneticist Michael Baraitser, of the Institute of Child Health. With colleagues Marcus Prembey and Jane Hurst, they started taking blood samples for analyses in 1987. Their first report in 1990 shows that 16 family members were affected by severe abnormality, though their intelligence and hearing are normal, and that the condition was genetically inherited (autosomal dominant).[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.[9][10] Her reports promulgated a notion of "grammar gene" and a controversial concept of grammar-specific disorder.[11][12]

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 normal 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 normal people. The underactive regions included motor neurons that control face and mouth regions. The areas that were overactive includes Broca's area, the speech centre.[13] With Oxford geneticists Simon Fisher and Anthony Monaco, they identified the exact location of the gene on the long arm of chromosome 7 (7q31) in 1998.[14] The chromosomal region (locus) was named SPCH1 (for speech-and-language-disorder-1), and it contains 70 genes.[15] 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, and that this gene plays a major role in the origin and development of language.[16] Mutations in the genes result in speech and language problems.[17][18][19]

See also

References
  1. Belton, Emma; Salmond, Claire H.; Watkins, Kate E.; Vargha-Khadem, Faraneh; Gadian, David G. (2003). "Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia". Human Brain Mapping. 18 (3): 194–200. doi:10.1002/hbm.10093. PMC 6872113. PMID 12599277.
  2. Nudel, Ron; Newbury, Dianne F (2013). "FOXP2". Wiley Interdisciplinary Reviews: Cognitive Science. 4 (5): 547–560. doi:10.1002/wcs.1247. PMC 3992897. PMID 24765219.
  3. Preuss, T. M. (2012). "Human brain evolution: From gene discovery to phenotype discovery". Proceedings of the National Academy of Sciences. 109 (Supplement_1): 10709–10716. doi:10.1073/pnas.1201894109. PMC 3386880. PMID 22723367.
  4. "Human Ape". natgeotv.com. NGC Europe Limited. Retrieved 31 October 2014.
  5. Taylor, Jeremy (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, Kate E; Gadian, David G.; Vargha-Khadem, Faraneh (1999). "Functional and Structural Brain Abnormalities Associated with a Genetic Disorder of Speech and Language". The American Journal of Human Genetics. 65 (5): 1215–1221. doi:10.1086/302631. PMC 1288272. PMID 10521285.
  7. Vargha-Khadem, F.; Watkins, K.; Alcock, K.; Fletcher, P.; Passingham, R. (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. 92 (3): 930–933. doi:10.1073/pnas.92.3.930. PMC 42734. PMID 7846081.
  8. Hurst, J. A.; Baraitser, M.; Auger, E.; Graham, F.; Norell, S. (1990). "An extended family with a dominantly inherited speech disorder". Developmental Medicine & Child Neurology. 32 (4): 352–355. doi:10.1111/j.1469-8749.1990.tb16948.x. PMID 2332125.
  9. Gopnik, M. (1990). "Genetic basis of grammar defect". Nature. 347 (6288): 26–26. doi:10.1038/347026a0. PMID 2395458.
  10. Gopnik, M. (1990). "Feature-blind grammar and dysphasia". Nature. 344 (6268): 715–715. doi:10.1038/344715a0. PMID 2330028.
  11. Cowie, Fiona (1999). What's Within?: Nativism Reconsidered. New York, US: Oxford University Press. pp. 290–291. ISBN 978-0-1951-5978-3.
  12. Jenkins, Lyle (2000). Biolinguistics: Exploring the Biology of Language (Revised ed.). Cambridge, UK: Cambridge University Press. pp. 98–99. ISBN 978-0-5210-0391-9.
  13. Vargha-Khadem, F.; Watkins, K. E.; Price, C. J.; Ashburner, J.; Alcock, K. J.; Connelly, A.; Frackowiak, R. S. J.; Friston, K. J.; Pembrey, M. E.; Mishkin, M.; Gadian, D. G.; Passingham, R. E. (1998). "Neural basis of an inherited speech and language disorder". Proceedings of the National Academy of Sciences. 95 (21): 12695–12700. doi:10.1073/pnas.95.21.12695. PMC 22893. PMID 9770548.
  14. Fisher, Simon E.; Vargha-Khadem, Faraneh; Watkins, Kate E.; Monaco, Anthony P.; Pembrey, Marcus E. (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.
  15. "Genes that are essential for speech". The Brain from Top to Bottom. Retrieved 31 October 2014.
  16. Lai, Cecilia S. L.; Fisher, Simon E.; Hurst, Jane A.; Vargha-Khadem, Faraneh; Monaco, Anthony P. (2001). "A forkhead-domain gene is mutated in a severe speech and language disorder". Nature. 413 (6855): 519–523. doi:10.1038/35097076. PMID 11586359.
  17. Braten, ed. by Stein (2007). On being moved : from mirror neurons to empathy. Amsterdam [u.a.]: John Benjamins Publication. ISBN 978-9-027252043.CS1 maint: extra text: authors list (link)
  18. Vargha-Khadem, Faraneh; Liegeois, Frederique (2007). "From speech to gene: The KE family and the FOXP2". In Braten, Stein (ed.). On Being Moved : From Mirror Neurons to Empathy. Amsterdam: John Benjamins Publication. p. 11. ISBN 978-9-027252043. OCLC 643718628.
  19. Fisher, Simon E.; Scharff, Constance (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. PMID 19304338.
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