Bilateral periventricular nodular heterotopia due to filamin 1 gene mutation: widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex

Kakita, Akiyoshi; Hayashi, Shigenari; Moro, Francesca; Guerrini, Renzo; Ozawa, Tsunenori; Ono, Koji; Kameyama, Shigeki; Walsh, Christopher A.; Takahashi, Hitoshi

doi:10.1007/s00401-002-0594-9

Cited by 86 publications

(45 citation statements)

References 41 publications

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“…This patient also had a V528M variant in FLNA that has been reported in a case of bilateral periventricular nodular heterotopia [24] and also as a functional polymorphism [25]. Novel variants in FOXP1 , ATRX , AUTS2 , CSMD1 were detected in Patient 8.…”

Section: Discussionmentioning

confidence: 52%

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

et al. 2014

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Developmental delay and/or intellectual disability (DD/ID) affects 1–3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81–84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.

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Section: Discussionmentioning

confidence: 52%

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

et al. 2014

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“…This function echoes vertebrate filamin activities. In contrast to Drosophila , mammals have three filamin proteins, A, B and C. Loss of function mutations in Filamin A are found in the human disease periventricular heterotopia, which is a defect in axonal migration that has been associated with the dynamic regulation of actin [62], [63], [64], [65]. However, detailed studies of patients carrying mutations shows evidence for a more complex regulation of axonal navigation than can be explained by simply an effect on growth cone motility [66], [67], [68].…”

Section: Discussionmentioning

confidence: 99%

Drosophila Ten-m and Filamin Affect Motor Neuron Growth Cone Guidance

et al. 2011

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The Drosophila Ten-m (also called Tenascin-major, or odd Oz (odz)) gene has been associated with a pair-rule phenotype. We identified and characterized new alleles of Drosophila Ten-m to establish that this gene is not responsible for segmentation defects but rather causes defects in motor neuron axon routing. In Ten-m mutants the inter-segmental nerve (ISN) often crosses segment boundaries and fasciculates with the ISN in the adjacent segment. Ten-m is expressed in the central nervous system and epidermal stripes during the stages when the growth cones of the neurons that form the ISN navigate to their targets. Over-expression of Ten-m in epidermal cells also leads to ISN misrouting. We also found that Filamin, an actin binding protein, physically interacts with the Ten-m protein. Mutations in cheerio, which encodes Filamin, cause defects in motor neuron axon routing like those of Ten-m. During embryonic development, the expression of Filamin and Ten-m partially overlap in ectodermal cells. These results suggest that Ten-m and Filamin in epidermal cells might together influence growth cone progression.

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“…These connectivity defects are theorized to interrupt the efficient communication between the cortical regions necessary for maintenance of reading fluency. Neuropathological studies have confirmed, among other abnormalities, alterations in white matter tracts in the vicinity of nodular heterotopia [10,11]. …”

Section: Introductionmentioning

confidence: 97%

Early cognitive and behavioral problems in children with nodular heterotopia

Felker

Walker

Sokol

et al. 2011

Epilepsy & Behavior

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Adults with periventricular nodular heterotopia (PNH) suffer from epilepsy and dyslexia but most have normal intelligence. It is not known whether PNH-related reading difficulty can be detected earlier in childhood, or whether associated behavioral problems are present. We studied 10 children with PNH, three of whom did not have seizures, and 10 matched controls with neuropsychological testing and parental rating instruments at two timepoints separated by about one year. Children with PNH performed significantly worse than controls on three tasks related to reading fluency. In addition, those with PNH showed significantly worse adaptive skills, and a measure of conduct problems significantly worsened over time. Mood and behavioral problems were reported more commonly, though not significantly so, in children with PNH. These findings demonstrate that reading dysfluency can be evident in children with nodular heterotopia, even in the absence of epilepsy, but also highlight difficulties with behavior in this population.

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Bilateral periventricular nodular heterotopia due to filamin 1 gene mutation: widespread glomeruloid microvascular anomaly and dysplastic cytoarchitecture in the cerebral cortex

Cited by 86 publications

References 41 publications

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel

Drosophila Ten-m and Filamin Affect Motor Neuron Growth Cone Guidance

Early cognitive and behavioral problems in children with nodular heterotopia

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