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Volney Sheen

Publications and source records attributed to Volney Sheen.

7 recordsLinked to original sources
PubMed2006

Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males.

We report on the case of dizygotic twin boys, born prematurely to an asymptomatic mother. Bilateral periventricular heterotopias with enlarged ventricles were discovered at birth in both twins. One of the twins died prematurely of bronchopulmonary complications, and was shown to have several neuropathological anomalies (microgyria, thin corpus callosum, and reduced white matter). The surviving twin had mental retardation, without epilepsy. MRI of the mother showed asymptomatic periventricular heterotopias without ventricular enlargement. She had two affected daughters also with asymptomatic periventricular heterotopias. A point mutation in the last coding exon 48 of the Filamin A (FLNA) gene (7922c > t) was discovered on sequencing and segregated with the affected individuals. This family has a classical X-linked dominant BPNH pathology, with greater severity in males than females. The location of the FLNA mutation is discussed in light of the neuropathological anomalies and mental retardation in male patients.

Amino Acid Sequence↗
PubMed2006

Overlapping expression of ARFGEF2 and Filamin A in the neuroependymal lining of the lateral ventricles: insights into the cause of periventricular heterotopia.

Periventricular heterotopia (PH) is a malformation of cortical development characterized by nodules of neurons, ectopically located along the lateral ventricles of the brain. Mutations in the vesicle transport ADP-ribosylation factor guanine exchange factor 2 gene (ARFGEF2) or the actin-binding Filamin A (FLNA) gene cause PH. Previous studies have shown that FLNA expression is developmentally regulated, with strongest expression observed along the ventricular zone (VZ) and to a lesser degree in postmitotic neurons in the cortex. Here we characterize the expression patterns for ARFGEF2 within the central nervous systems of human and mouse in order to better understand their potential roles in causing PH. ARFGEF2 mRNA was widely expressed in all cortical layers, especially in the neural precursors of the ventricular and subventricular zones (SVZ) during development, with persistent but diminished expression in adulthood. ARFGEF2 encodes for the protein brefeldin-inhibited guanine exchange factor 2 (BIG2). BIG2 protein immunoreactivity was most strongly localized to the neural progenitors along the neuroependymal lining of the VZ during development, with decreased expression in adulthood. Furthermore, overlapping BIG2 and FLNA expression was greatest in these same neuroependymal cells of human embryonic brain and was co-expressed in progenitors by Western blot. Finally, transfection of a dominant-negative construct of ARFGEF2 in SHSY5Y neuroblastoma cells partially blocked FLNA transport from the Golgi apparatus to the cell membrane. These results suggest that mutations in ARFGEF2 may impair targeted transport of FLNA to the cell surface within neural progenitors along the neuroependyma and that disruption of these cells could contribute to PH formation.

Animals↗
PubMed2006

Cerebral developmental disorders.

PURPOSE OF REVIEW: The development of the cerebral cortex progresses through defined stages including neural proliferation, neuroblast migration and neuronal differentiation. Disruptions in each of these developmental stages can lead to characteristic cerebral cortical malformations. This review provides an overview of the known genetic causes of human cerebral developmental disorders and discusses the potential molecular mechanisms that contribute to these malformations. RECENT FINDINGS: Mutations in genes that are involved in neural proliferation give rise to microcephaly (small brain). Mutations in genes that direct the onset of neuroblast migration give rise to periventricular heterotopia (clusters of neurons along the ventricles of the brain). Mutations in genes that are required for neuroblast migration cause type I lissencephaly (smooth brain) and subcortical band heterotopia (smooth brain with a band of neurons beneath the cortex). Mutations in genes that direct migratory neurons to arrest in the cortex lead to type II lissencephaly (smooth brain with clusters of neurons along the surface of the brain). SUMMARY: The identification of causative genes involved in the formation of the cerebral cortex now allows for a rational approach with which to interpret the underlying mechanistic basis for many of these disorders.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Mutation in filamin A causes periventricular heterotopia, developmental regression, and West syndrome in males.

PURPOSE: Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray-matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant pattern. Heterozygotic female patients usually remain asymptomatic until the second or third decade of life, when they may have predominantly focal seizures, whereas hemizygotic male fetuses typically die in utero. Recent studies have also reported mutations in FLNA in male patients with PH who are cognitively normal. We describe PH in three male siblings with PH due to FLNA, severe developmental regression, and West syndrome. METHODS: The study includes the three affected brothers and their parents. Video-EEG recordings and magnetic resonance image (MRI) scanning were performed on all individuals. Mutations for FLNA were detected by using polymerase chain reaction (PCR) on genomic DNA followed by single-stranded conformational polymorphism (SSCP) analysis or sequencing. RESULTS: Two of the siblings are monozygotic twins, and all had West syndrome with hypsarrhythmia on EEG. MRI of the brain revealed periventricular nodules of cerebral gray-matter intensity, typical for PH. Mutational analyses demonstrated a cytosine-to-thymidine missense mutation (c. C1286T), resulting in a threonine-to-methionine amino acid substitution in exon 9 of the FLNA gene. CONCLUSIONS: The association between PH and West syndrome, to our knowledge, has not been previously reported. Males with PH have been known to harbor FLNA mutations, although uniformly, they either show early lethality or survive and have a normal intellect. The current studies show that FLNA mutations can cause periventricular heterotopia, developmental regression, and West syndrome in male patients, suggesting that this type of FLNA mutation may contribute to severe neurologic deficits.

Brain Diseases↗
PubMed2005

Periventricular heterotopia.

Periventricular heterotopia (PH) is clinically diagnosed on the basis of the radiographic characteristics of heterotopic nodules composed of disorganized neurons along the lateral ventricles of the brain. Epilepsy is the main presenting symptom of patients with PH. Behaviorally, patients generally are of normal intelligence, although there have been associated findings of learning disabilities, namely, dyslexia. Two genes responsible for PH have been identified: FilaminA, which encodes for the protein filamin A, and ARFGEF2, which encodes for the vesical transport-regulating protein ARFGEF2. The much more common X-linked dominant form of this disorder is due to filamin A, affects females, and is typically lethal in males. A much rarer autosomal recessive form due to ARFGEF2 mutations leads to microcephaly and developmental delay in addition to PH. Cell motility, adhesion defects, and weakening along the neuroepithelial lining may result from defects in these genes during cortical development and contribute to PH, but the mechanisms are not clear yet. Treatment of PH is largely symptomatic, following basic principles for epilepsy management and genetic counseling.

Animals↗