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TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins.

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TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. / Kumar, Ravinesh A; Pilz, Daniela T; Babatz, Timothy D; Cushion, Thomas D; Harvey, Kirsten; Topf, Maya; Yates, Laura; Robb, Stephanie; Uyanik, Gökhan; Mancini, Gracia M S; Rees, Mark I; Harvey, Robert J; Dobyns, William B.

In: HUM MOL GENET, Vol. 19, No. 14, 14, 2010, p. 2817-2827.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Kumar, RA, Pilz, DT, Babatz, TD, Cushion, TD, Harvey, K, Topf, M, Yates, L, Robb, S, Uyanik, G, Mancini, GMS, Rees, MI, Harvey, RJ & Dobyns, WB 2010, 'TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins.', HUM MOL GENET, vol. 19, no. 14, 14, pp. 2817-2827. <http://www.ncbi.nlm.nih.gov/pubmed/20466733?dopt=Citation>

APA

Kumar, R. A., Pilz, D. T., Babatz, T. D., Cushion, T. D., Harvey, K., Topf, M., Yates, L., Robb, S., Uyanik, G., Mancini, G. M. S., Rees, M. I., Harvey, R. J., & Dobyns, W. B. (2010). TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. HUM MOL GENET, 19(14), 2817-2827. [14]. http://www.ncbi.nlm.nih.gov/pubmed/20466733?dopt=Citation

Vancouver

Kumar RA, Pilz DT, Babatz TD, Cushion TD, Harvey K, Topf M et al. TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins. HUM MOL GENET. 2010;19(14):2817-2827. 14.

Bibtex

@article{e3c87a8b3b3b4e16bb5089d25aae7f27,
title = "TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins.",
abstract = "We previously showed that mutations in LIS1 and DCX account for approximately 85% of patients with the classic form of lissencephaly (LIS). Some rare forms of LIS are associated with a disproportionately small cerebellum, referred to as lissencephaly with cerebellar hypoplasia (LCH). Tubulin alpha1A (TUBA1A), encoding a critical structural subunit of microtubules, has recently been implicated in LIS. Here, we screen the largest cohort of unexplained LIS patients examined to date to determine: (i) the frequency of TUBA1A mutations in patients with lissencephaly, (ii) the spectrum of phenotypes associated with TUBA1A mutations and (iii) the functional consequences of different TUBA1A mutations on microtubule function. We identified novel and recurrent TUBA1A mutations in approximately 1% of children with classic LIS and in approximately 30% of children with LCH, making this the first major gene associated with the rare LCH phenotype. We also unexpectedly found a TUBA1A mutation in one child with agenesis of the corpus callosum and cerebellar hypoplasia without LIS. Thus, our data demonstrate a wider spectrum of phenotypes than previously reported and allow us to propose new recommendations for clinical testing. We also provide cellular and structural data suggesting that LIS-associated mutations of TUBA1A operate via diverse mechanisms that include disruption of binding sites for microtubule-associated proteins (MAPs).",
keywords = "Humans, Male, Female, Child, Cells, Cultured, Brain pathology, Models, Molecular, Polymorphism, Single Nucleotide, Signal Transduction genetics, Mutation physiology, Neurons metabolism, Transfection, Cell Movement genetics, Genetic Association Studies, Lissencephaly genetics, Protein Binding genetics, Protein Structure, Secondary genetics, Tubulin chemistry, Humans, Male, Female, Child, Cells, Cultured, Brain pathology, Models, Molecular, Polymorphism, Single Nucleotide, Signal Transduction genetics, Mutation physiology, Neurons metabolism, Transfection, Cell Movement genetics, Genetic Association Studies, Lissencephaly genetics, Protein Binding genetics, Protein Structure, Secondary genetics, Tubulin chemistry",
author = "Kumar, {Ravinesh A} and Pilz, {Daniela T} and Babatz, {Timothy D} and Cushion, {Thomas D} and Kirsten Harvey and Maya Topf and Laura Yates and Stephanie Robb and G{\"o}khan Uyanik and Mancini, {Gracia M S} and Rees, {Mark I} and Harvey, {Robert J} and Dobyns, {William B}",
year = "2010",
language = "Deutsch",
volume = "19",
pages = "2817--2827",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "14",

}

RIS

TY - JOUR

T1 - TUBA1A mutations cause wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge on alpha tubulins.

AU - Kumar, Ravinesh A

AU - Pilz, Daniela T

AU - Babatz, Timothy D

AU - Cushion, Thomas D

AU - Harvey, Kirsten

AU - Topf, Maya

AU - Yates, Laura

AU - Robb, Stephanie

AU - Uyanik, Gökhan

AU - Mancini, Gracia M S

AU - Rees, Mark I

AU - Harvey, Robert J

AU - Dobyns, William B

PY - 2010

Y1 - 2010

N2 - We previously showed that mutations in LIS1 and DCX account for approximately 85% of patients with the classic form of lissencephaly (LIS). Some rare forms of LIS are associated with a disproportionately small cerebellum, referred to as lissencephaly with cerebellar hypoplasia (LCH). Tubulin alpha1A (TUBA1A), encoding a critical structural subunit of microtubules, has recently been implicated in LIS. Here, we screen the largest cohort of unexplained LIS patients examined to date to determine: (i) the frequency of TUBA1A mutations in patients with lissencephaly, (ii) the spectrum of phenotypes associated with TUBA1A mutations and (iii) the functional consequences of different TUBA1A mutations on microtubule function. We identified novel and recurrent TUBA1A mutations in approximately 1% of children with classic LIS and in approximately 30% of children with LCH, making this the first major gene associated with the rare LCH phenotype. We also unexpectedly found a TUBA1A mutation in one child with agenesis of the corpus callosum and cerebellar hypoplasia without LIS. Thus, our data demonstrate a wider spectrum of phenotypes than previously reported and allow us to propose new recommendations for clinical testing. We also provide cellular and structural data suggesting that LIS-associated mutations of TUBA1A operate via diverse mechanisms that include disruption of binding sites for microtubule-associated proteins (MAPs).

AB - We previously showed that mutations in LIS1 and DCX account for approximately 85% of patients with the classic form of lissencephaly (LIS). Some rare forms of LIS are associated with a disproportionately small cerebellum, referred to as lissencephaly with cerebellar hypoplasia (LCH). Tubulin alpha1A (TUBA1A), encoding a critical structural subunit of microtubules, has recently been implicated in LIS. Here, we screen the largest cohort of unexplained LIS patients examined to date to determine: (i) the frequency of TUBA1A mutations in patients with lissencephaly, (ii) the spectrum of phenotypes associated with TUBA1A mutations and (iii) the functional consequences of different TUBA1A mutations on microtubule function. We identified novel and recurrent TUBA1A mutations in approximately 1% of children with classic LIS and in approximately 30% of children with LCH, making this the first major gene associated with the rare LCH phenotype. We also unexpectedly found a TUBA1A mutation in one child with agenesis of the corpus callosum and cerebellar hypoplasia without LIS. Thus, our data demonstrate a wider spectrum of phenotypes than previously reported and allow us to propose new recommendations for clinical testing. We also provide cellular and structural data suggesting that LIS-associated mutations of TUBA1A operate via diverse mechanisms that include disruption of binding sites for microtubule-associated proteins (MAPs).

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Cells, Cultured

KW - Brain pathology

KW - Models, Molecular

KW - Polymorphism, Single Nucleotide

KW - Signal Transduction genetics

KW - Mutation physiology

KW - Neurons metabolism

KW - Transfection

KW - Cell Movement genetics

KW - Genetic Association Studies

KW - Lissencephaly genetics

KW - Protein Binding genetics

KW - Protein Structure, Secondary genetics

KW - Tubulin chemistry

KW - Humans

KW - Male

KW - Female

KW - Child

KW - Cells, Cultured

KW - Brain pathology

KW - Models, Molecular

KW - Polymorphism, Single Nucleotide

KW - Signal Transduction genetics

KW - Mutation physiology

KW - Neurons metabolism

KW - Transfection

KW - Cell Movement genetics

KW - Genetic Association Studies

KW - Lissencephaly genetics

KW - Protein Binding genetics

KW - Protein Structure, Secondary genetics

KW - Tubulin chemistry

M3 - SCORING: Zeitschriftenaufsatz

VL - 19

SP - 2817

EP - 2827

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 14

M1 - 14

ER -