Lissencephaly and Mild Cerebellar Vermis Hypoplasia in a Case of Microcephaly and Chorioretinal Dysplasia

Lee, Byung‐Joo; Kim, Jeong Hun; Yu, Young Suk

doi:10.3109/13816811003620509

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…It has been suggested that abnormal findings of brain anatomy including cerebral atrophy, cortical dysplasia, myelination delay and white matter hypoplasia are more significantly correlated with poor developmental performance than the severity of microcephaly 10 . Brain abnormalities including pachymicrogyria 11 and lissencephaly 12,13 have been reported in association with MCLMR. It is thought that the developmental anomalies in the retina could be analogous to central nervous system anomalies.…”

Section: Discussionmentioning

confidence: 99%

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

et al. 2013

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Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.

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Section: Discussionmentioning

confidence: 99%

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

et al. 2013

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“…Lissencephaly is a cortical malformation characterized by a ‘smooth cortex’ that arises from the disruption of normal development ( des Portes et al, 1998 ; Deuel et al, 2006 ; Francis et al, 1999 ; Gleeson et al, 1998 ). Patients with lissencephaly often have an associated microcephaly indicating defects in neural progenitor proliferation ( Lee et al, 2010 ; Pramparo et al, 2010 ). Furthermore, the ‘smooth’ brain is the result of abnormal neuronal migration, which causes an abnormally thick four-layered cortex ( Dobyns et al, 1984 ; Jellinger and Rett, 1976 ), and many patients with lissencephaly also have a reduction or absence of major axon tracts, indicating problems with axon guidance or outgrowth ( Kappeler et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking

Rao

Liu

et al. 2022

eLife

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Mutations in the microtubule (MT)-binding protein doublecortin (DCX) or in the MT-based molecular motor dynein result in lissencephaly. However, a functional link between DCX and dynein has not been defined. Here, we demonstrate that DCX negatively regulates dynein-mediated retrograde transport in neurons from Dcx-/y or Dcx-/y;Dclk1-/- mice by reducing dynein's association with MTs and by disrupting the composition of the dynein motor complex. Previous work showed an increased binding of the adaptor protein C-Jun-amino-terminal kinase-interacting protein 3 (JIP3) to dynein in the absence of DCX. Using purified components, we demonstrate that JIP3 forms an active motor complex with dynein and its cofactor dynactin with two dyneins per complex. DCX competes with the binding of the second dynein, resulting in a velocity reduction of the complex. We conclude that DCX negatively regulates dynein-mediated retrograde transport through two critical interactions by regulating dynein binding to MTs and by regulating the composition of the dynein motor complex.

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“…Lissencephaly is a cortical malformation characterized by a “smooth cortex” which arises from disruption of normal development (des Portes et al, 1998; Deuel et al, 2006; Francis et al, 1999; Gleeson et al, 1998). Patients with lissencephaly often have an associated microcephaly indicating defects in neural progenitor proliferation (Lee et al, 2010; Pramparo et al, 2010). Furthermore, the “smooth” brain is the result of abnormal neuronal migration, which causes an abnormally thick 4-layered cortex (Dobyns et al, 1984; Jellinger and Rett, 1976), and many patients with lissencephaly also have a reduction or absence of major axon tracts indicating problems with axon guidance or outgrowth (Kappeler et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking

Rao

Liu

et al. 2022

Preprint

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Mutations in the microtubule (MT)-binding protein doublecortin (DCX) or in the MT-based molecular motor dynein result in lissencephaly. However, a functional link between DCX and dynein has not been defined. Here, we demonstrate that DCX negatively regulates dynein-mediated retrograde transport by reducing dynein's association with MTs and by disrupting the composition of the dynein motor complex. Previous work showed an increased binding of the adaptor protein C-Jun-amino-terminal kinase-interacting protein 3 (JIP3) to dynein in the absence of DCX. Using purified components, we demonstrate that JIP3 forms an active motor complex with dynein and its cofactor dynactin with two dyneins per complex. DCX competes with the binding of the second dynein, resulting in a velocity reduction of the complex. We conclude that DCX negatively regulates dynein-mediated retrograde transport through two critical interactions by regulating dynein binding to MTs and by regulating the association of JIP3 to the dynein motor complex.

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Lissencephaly and Mild Cerebellar Vermis Hypoplasia in a Case of Microcephaly and Chorioretinal Dysplasia

Abstract: These results show that microcephaly and chorioretinal dysplasia can be accompanied by lissencephaly, thus brain imaging should be considered in evaluating these patients.

Cited by 5 publications

References 36 publications

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking

Doublecortin and JIP3 are neural-specific counteracting regulators of dynein-mediated retrograde trafficking

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