Abstract:
:The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and microtubule-associated components such as doublecortin, and LIS1. Mutations in these genes are associated with the anatomical abnormality lissencephaly, which is believed to reflect failure of neuronal migration. An important recent observation has been the dependence of cortical neuronal migration upon acetylation of alpha-tubulin at lysine 40 by the histone acetyltransferase Elongator complex. Here, we describe a recognizable autosomal recessive syndrome, characterized by generalized polymicrogyria in association with optic nerve hypoplasia (PMGOH). By autozygosity mapping, we show that the molecular basis for this condition is mutation of the TUBA8 gene, encoding a variant alpha-tubulin of unknown function that is not susceptible to the lysine 40 acetylation that regulates microtubule function during cortical neuron migration. Together with the unique expression pattern of TUBA8 within the developing cerebral cortex, these observations suggest a role for this atypical microtubule component in regulating mammalian brain development.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Abdollahi MR,Morrison E,Sirey T,Molnar Z,Hayward BE,Carr IM,Springell K,Woods CG,Ahmed M,Hattingh L,Corry P,Pilz DT,Stoodley N,Crow Y,Taylor GR,Bonthron DT,Sheridan Edoi
10.1016/j.ajhg.2009.10.007subject
Has Abstractpub_date
2009-11-01 00:00:00pages
737-44issue
5eissn
0002-9297issn
1537-6605pii
S0002-9297(09)00462-5journal_volume
85pub_type
杂志文章abstract::The association between normal alleles at the CTG repeat and two nearby polymorphisms in the myotonin protein kinase gene, the Alu insertion/deletion polymorphism and the myotonic dystrophy kinase (DMK)(G/T) intron 9/HinfI polymorphism, has been analyzed in South African Negroids, a population in which myotonic dystro...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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doi:
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.12.007
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journal_title:American journal of human genetics
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doi:
更新日期:1994-07-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/380311
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
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journal_title:American journal of human genetics
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doi:
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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