Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia

Tentler, Dmitri; Gustavsson, Peter; Leisti, J; Schueler, Mary G.; Chelly, Jamel; Timonen, Eija; Annerén, Göran; Willard, Huntington F.; Dahl, Niklas

doi:10.1038/sj.ejhg.5200320

Cited by 52 publications

(43 citation statements)

References 20 publications

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“…However, it is also clear CVH can also be distinct from DWM. For example, mutations in Oligophrenin 1 (OPHN1), a widely expressed gene encoding a rhoGAP protein, cause X-linked mental retardation and CVH, but never DWM [62][63][64]. In vitro and in vivo experiments have demonstrated a role for Ophn1 in dendritic spine morphogensis in hippocampal neurons in mice, although no gross cerebellar anatomical abnormalities were observed in Ophn1 mutant mice [65,66].…”

Section: Dandy-walker Malformation and Cerebellar Vermis Hypoplasiamentioning

confidence: 99%

Cerebellar development and disease

Millen¹,

Gleeson²

2008

Current Opinion in Neurobiology

168

141

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The molecular control of cell type specification within the developing cerebellum as well as the genetic causes of the most common human developmental cerebellar disorders have long remained mysterious. Recent genetic lineage and loss-of-function data from mice have revealed unique and non-overlapping anatomical origins for GABAergic neurons from ventricular zone precursors and glutamatergic cell from rhombic lip precursors, mirroring distinct origins for these neurotransmitterspecific cell types in the cerebral cortex. Mouse studies elucidating the role of Ptf1a as a cerebellar ventricular zone GABerigic fate switch were actually preceded by the recognition that PTF1A mutations in humans cause cerebellar agenesis, a birth defect of the human cerebellum. Indeed, several genes for congenital human cerebellar malformations have recently been identified, including genes causing Joubert syndrome, Dandy-Walker malformation and Ponto-cerebellar hypoplasia. These studies have pointed to surprisingly complex roles for transcriptional regulation, mitochondrial function and neuronal cilia in patterning, homeostasis and cell proliferation during cerebellar development. Together mouse and human studies are synergistically advancing our understanding of the developmental mechanisms that generate the uniquely complex mature cerebellum.

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Section: Dandy-walker Malformation and Cerebellar Vermis Hypoplasiamentioning

confidence: 99%

Cerebellar development and disease

Millen¹,

Gleeson²

2008

Current Opinion in Neurobiology

168

141

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“…More recently, however, the presence of OPHN1 mutations have as well been documented in families with syndromic forms of MR. Most of these patients share in common that in addition to cognitive impairment, they display cerebellar hypoplasia with vermian dysplasia and/or epilepsy [5,66,79,90]. In addition, some of these patients showed signs of strabismus, macrocephaly, hypogenitalism, hyperactivity, anxiety, and in some rare cases ataxia.…”

Section: Oligophrenin-1mentioning

confidence: 99%

Rho-linked genes and neurological disorders

Kasri

Aelst

2007

Pflugers Arch - Eur J Physiol

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Mental retardation (MR) is a common cause of intellectual disability and affects approximately 2 to 3 % of children and young adults. MR has been consistently associated with changes in dendrites and dendritic spine structure. Given that dendritic spine morphology has been tightly linked to synaptic activity, altered spine morphology has been suggested to be the underlying cause of cognitive disabilities observed in MR. The structure and dynamics of dendritic spines is determined by its underlying actin cytoskeleton. Signaling molecules and cascades important for cytoskeletal regulation have therefore naturally attracted a great deal of attention. As key regulators of both the actin and microtubule cytoskeletons, it is not surprising that the Rho GTPases have emerged as important regulators of dendrite and spine structural plasticity. In support of this, mutations in regulators and effectors of Rho GTPases have been associated with diseases affecting the nervous system, including MR and amyotropic lateral sclerosis (ALS). Here we will discuss Rho GTPase related genes and their signaling pathways involved in MR and ALS.

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“…Subsequently OPHN1 mutations were identified in families with intellectual disability associated with cerebellar hypoplasia or epilepsy [9][10][11] .…”

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confidence: 99%