Missense mutations resulting in type 1 lissencephaly

Reiner, Orly; Coquelle, Frédéric M.

doi:10.1007/s00018-004-4344-0

Cited by 13 publications

(5 citation statements)

References 156 publications

(194 reference statements)

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“…Mutation(s) in the LIS1 gene or the X-linked gene doublecortin (DCX) results in a spectrum of disorders, including lissencephaly or 'smooth brain,' due to malfunctioning of key proteins. [6,7] Similar results were seen in our patient, as DCX missense mutation would have resulted into malfunctioning of key proteins, leading to lissencephaly. Since it was a gene mutation, the treatment was focused on management of seizures and therapies-typically physical and occupational therapies -for building muscle strength.…”

Section: Resultssupporting

confidence: 81%

Lissencephaly child showing FISH negative and mutation in DCX gene with normal parental genetic makeup

Gupta¹,

Verma²,

Raina³

et al. 2006

Indian J Hum Genet

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Lissencephaly is a clinically and genetically heterogeneous malformation of the brain, leading to a severe disabling condition and seizures. The recent discovery of molecular techniques and identification of lissencephaly genes (LIS 1 and DCX) has allowed etiologic diagnosis of this disorder. We describe a patient with lissencephaly in whom fluorescence in situ hybridization and DCX mutation analysis determined etiologic diagnosis, allowing precise genetic counseling and providing prenatal diagnosis for the family.

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Section: Resultssupporting

confidence: 81%

Lissencephaly child showing FISH negative and mutation in DCX gene with normal parental genetic makeup

Gupta¹,

Verma²,

Raina³

et al. 2006

Indian J Hum Genet

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“…Mutations in the X-linked gene doublecortin (DCX) result in lissencephaly or subcortical band heterotopia (SBH) [ 1 , 2 ] (see review in [ 3 ]). Lissencephaly is a severe brain malformation characterized by absent (agyria) or decreased (pachygyria) convolutions accompanied by thickening of the cortex [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The evolving doublecortin (DCX) superfamily

et al. 2006

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Background: Doublecortin (DCX) domains serve as protein-interaction platforms. Mutations in members of this protein superfamily are linked to several genetic diseases. Mutations in the human DCX gene result in abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, and DCDC2 has been associated with dyslectic reading disabilities.

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“…Abnormalities in the migration of neurons into the embryonic cortex lead in extreme cases to loss of normal convolutions of the cortex in humans, known as lissencephaly ('smooth brain'). 1 Mutations in LIS1, an autosomal gene located on chromosome 17p13.3, 2 are known to result in lissencephaly. The deduced amino acid sequence places LIS1 as a member of the WD (tryptophan-aspartic acid) repeat family of proteins.…”

Section: Introductionmentioning

confidence: 99%

Novel Functional Features of the LIS-H Domain: Role in Protein Dimerization, Half-Life and Cellular Localization

Gerlitz¹,

Darhin²,

Giorgio³

et al. 2005

Cell Cycle

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The presence of a conserved protein motif usually implies common functional features. Here, we focused on the LisH (LIS1 homology) domain, which is found in multiple proteins, and have focused on three involved in human genetic diseases; LIS1, Transducin beta-like 1X (TBL1) and Oral-facial-digital type 1 (OFD1). The recently solved structure of the LisH domain in the N-terminal region of LIS1 depicted it as a novel dimerization motif. Our findings indicated that the LisH domain of both LIS1 and TBL1 is essential for in vitro oligomerization. Furthermore, our study disclosed novel in vivo features of the LisH motif. Mutations in conserved LisH amino acids significantly reduced both the protein half-life of LIS1, TBL1, and OFD1, and dramatically affected specific intracellular localizations of these proteins. LIS1 mutated in the LisH domain induced its localization to the actin filaments. TBL1 mutated in the LisH domain was not imported into the nucleus. Mutations in OFD1 modified its localization to the Golgi apparatus and in some cases also to the nucleus. In summary, the LisH domain may participate in protein dimerization, affect protein half-life, and may influence specific cellular localizations. Our results allow the prediction that mutations within the LisH motif are likely to result in pathogenic consequences in genes associated with genetic diseases.

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Missense mutations resulting in type 1 lissencephaly

Cited by 13 publications

References 156 publications

Lissencephaly child showing FISH negative and mutation in DCX gene with normal parental genetic makeup

Lissencephaly child showing FISH negative and mutation in DCX gene with normal parental genetic makeup

The evolving doublecortin (DCX) superfamily

Novel Functional Features of the LIS-H Domain: Role in Protein Dimerization, Half-Life and Cellular Localization

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