The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism

Castermans, Dries; Wilquet, Valérie; Parthoens, Eef; Huysmans, Christel; Steyaert, Jean; Swinnen, Lode J.; Jp, Fryns; Ven, Willem Van de; Devriendt, Koenraad

doi:10.1136/jmg.40.5.352

Cited by 127 publications

(99 citation statements)

References 13 publications

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“…A recent report links a case of sporadic autism to interruption of the nbea locus by a chromosomal translocation. No evaluation of nbea expression was possible in this case, and expression of other genes in the vicinity of the translocation was not determined (Castermans et al, 2003). A search of the literature (Gilbert et al, 1999) failed to reveal any other genetic mutations (mouse or human) that map to the mouse or human nbea loci.…”

Section: Neurobeachin Structure and Functionmentioning

confidence: 99%

Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Su¹,

Balice-Gordon²,

Hess³

et al. 2004

J. Neurosci.

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We report a random disruption in the mouse genome that resulted in lethal paralysis in homozygous newborns. The disruption blocked expression of neurobeachin, a protein containing a BEACH (beige and Chediak-Higashi) domain implicated in synaptic vesicle trafficking and an AKAP (A-kinase anchor protein) domain linked to localization of cAMP-dependent protein kinase activity. nbea-null mice demonstrated a complete block of evoked synaptic transmission at neuromuscular junctions, whereas nerve conduction, synaptic structure, and spontaneous synaptic vesicle release were completely normal. These findings support an essential role for neurobeachin in evoked neurotransmitter release at neuromuscular junctions and suggest that it plays an important role in synaptic transmission.

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Section: Neurobeachin Structure and Functionmentioning

confidence: 99%

Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Su¹,

Balice-Gordon²,

Hess³

et al. 2004

J. Neurosci.

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“…6 aCGH and real-time quantitative PCR (RTQ-PCR) analyses were performed as described. 3,7 Specific primers used for RTQ-PCR are listed as supplementary data.…”

Section: Molecular Analysismentioning

confidence: 99%

Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism

et al. 2008

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We describe an individual with autism and a coloboma of the eye carrying a mosaicism for a ring chromosome consisting of an inverted duplication of proximal chromosome 14. Of interest, the ring formation was associated with silencing of the amisyn gene present in two copies on the ring chromosome and located at 300 kb from the breakpoint. This observation lends further support for a locus for autism on proximal chromosome 14. Moreover, this case suggests that position effects need to be taken into account, when analyzing genotype -phenotype correlations based on chromosomal imbalances.

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“…Whereas NBEA is known for its neuronal function and its implication in autism spectrum disorders (Castermans et al, 2003;Volders et al, 2011), the human homolog LRBA has a broad expression pattern, and its function is currently unknown (Wang et al, 2001). Both NBEA and LRBA have been linked to cancer (Wang et al, 2001(Wang et al, , 2004O'Neal et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Drosophila rugoseIs a Functional Homolog of MammalianNeurobeachinand Affects Synaptic Architecture, Brain Morphology, and Associative Learning

Volders

Scholz²,

Slabbaert

et al. 2012

J. Neurosci.

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Neurobeachin (Nbea) is implicated in vesicle trafficking in the regulatory secretory pathway, but details on its molecular function are currently unknown. We have used Drosophila melanogaster mutants for rugose (rg), the Drosophila homolog of Nbea, to further elucidate the function of this multidomain protein. Rg is expressed in a granular pattern reminiscent of the Golgi network in neuronal cell bodies and colocalizes with transgenic Nbea, suggesting a function in secretory regulation. In contrast to Nbea Ϫ/Ϫ mice, rg null mutants are viable and fertile and exhibit aberrant associative odor learning, changes in gross brain morphology, and synaptic architecture as determined at the larval neuromuscular junction. At the same time, basal synaptic transmission is essentially unaffected, suggesting that structural and functional aspects are separable. Rg phenotypes can be rescued by a Drosophila rg؉ transgene, whereas a mouse Nbea transgene rescues aversive odor learning and synaptic architecture; it fails to rescue brain morphology and appetitive odor learning. This dissociation between the functional redundancy of either the mouse or the fly transgene suggests that their complex composition of numerous functional and highly conserved domains support independent functions. We propose that the detailed compendium of phenotypes exhibited by the Drosophila rg null mutant provided here will serve as a test bed for dissecting the different functional domains of BEACH (for beige and human Chediak-Higashi syndrome) proteins, such as Rugose, mouse Nbea, or Nbea orthologs in other species, such as human.

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The neurobeachin gene is disrupted by a translocation in a patient with idiopathic autism

Cited by 127 publications

References 13 publications

Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Neurobeachin Is Essential for Neuromuscular Synaptic Transmission

Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism

Drosophila rugoseIs a Functional Homolog of MammalianNeurobeachinand Affects Synaptic Architecture, Brain Morphology, and Associative Learning

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