Molecular genetic delineation of a deletion of chromosome 13q12→q13 in a patient with autism and auditory processing deficits

Smith, Moyra; Woodroffe, Abigail; Smith, Rosemary J.; Holguin, S.; Martínez, Josefina Lozano; Filipek, Pauline A.; Modahl, Charlotte; Moore, B. P. L.; Bocian, Maureen; Mays, Lee Z; Laulhere, Tracy M.; Flodman, Pamela; Spence, M. Anne

doi:10.1159/000071040

Cited by 47 publications

(33 citation statements)

References 24 publications

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“…In a case report regarding autism and language deficits caused by auditory processing defects, Smith et al [42] reported the discovery of a 9-Mb region that was deleted in the 13q12 q13 region of chromosome 13. RGC-32 is one of the 27 genes that mapped within the deleted region, suggesting that it may function in brain development, and particularly in auditory processing.…”

Section: Rgc−32 and Other Diseasesmentioning

confidence: 99%

Role of response gene to complement 32 in diseases

Vlaicu

Cudrici

Ito

et al. 2008

Arch. Immunol. Ther. Exp.

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The role of response gene to complement (RGC)-32 as a cell cycle regulator has been attributed to its ability to activate cdc2 kinases and to induce S-phase entry and mitosis. However, recent studies revealed novel functions for RGC-32 in diverse processes such as cellular differentiation, inflammation, and fibrosis. Besides responding to C5b-9 stimulation, RGC-32 expression is also induced by growth factors, hormones, and cytokines. Transforming growth factor beta activates RGC-32 through Smad and RhoA signaling, thus initiating smooth muscle cell differentiation. Accumulating evidence has drawn attention to the deregulated expression of RGC-32 in human malignancies, hyper-immunoglobulin E syndrome, and fibrosis. RCG-32 expression is up-regulated in cutaneous T cell lymphoma and colon, ovarian, and breast cancer, but down-regulated in invasive prostate cancer, multiple myeloma, and drug-resistant glioblastoma. A better understanding of the mechanism by which RGC-32 contributes to the pathogenesis of these diseases will provide new insights into its therapeutic potential. In this review we provide an overview of this field and discuss the most recent research on RGC-32.

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Section: Rgc−32 and Other Diseasesmentioning

confidence: 99%

Role of response gene to complement 32 in diseases

Vlaicu

Cudrici

Ito

et al. 2008

Arch. Immunol. Ther. Exp.

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“…auditory behavior ͉ auditory brainstem responses ͉ auditory cortex ͉ autism ͉ language learning impairment C linical and epidemiological studies of language impairment and autism have shown a strong genetic component with multiple genes involved (1)(2)(3). The distributed complex of brain system abnormalities, however, also indicates that exposure to environmental factors at early stages of brain development may be a contributing or even causal factor in a significant percentage of cases.…”

mentioning

confidence: 99%

Perinatal anoxia degrades auditory system function in rats

Strata

Deipolyi²,

Bonham³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Little is known about the neural bases of the reduced auditory and cortical processing speeds that have been recorded in languageimpaired, autistic, schizophrenic, and other disabled human populations. Although there is strong evidence for genetic contributions to etiologies, epigenetic factors such as perinatal anoxia (PA) have been argued to be contributors, or causal, in a significant proportion of cases. In this article, we explored the consequences of PA on this elementary aspect of auditory behavior and on auditory system function in rats that were briefly perinatally anoxic. PA rats had increased acoustic thresholds and reduced processing efficiencies recorded in an auditory behavioral task. These rats had modestly increased interpeak intervals in their auditory brainstem responses, and substantially longer latencies in poststimulus time histogram responses recorded in the primary auditory cortex. The latter were associated with degraded primary auditory cortex receptive fields and a disrupted tonotopy. These processing deficits are consistent with the parallel behavioral and physiological deficits recorded in children and adults with a history of language-learning impairment and autism.auditory behavior ͉ auditory brainstem responses ͉ auditory cortex ͉ autism ͉ language learning impairment

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“…The karyotype of this patient showed a deletion involving 13q13 and portions of q12 and q14 which was not present in an autistic maternal cousin. The deletion in the second patient encompassed a 9Mb fragment in the 13q12-q13 region which was paternally derived [33]. It was not reported whether the father also showed autistic features.…”

Section: The Identification Of Neurobeachin As a Candidate Gene For Amentioning

confidence: 93%

“…1A) [33][34][35]. The initial deletion was described in a woman with autism, sporadic retinoblastoma and a reduced esterase D activity [35].…”

Section: The Identification Of Neurobeachin As a Candidate Gene For Amentioning

confidence: 99%

The Autism Candidate Gene Neurobeachin Encodes a Scaffolding Protein Implicated in Membrane Trafficking and Signaling

Volders

Nuytens²,

Creemers³

2011

CMM

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Autism is a developmental disorder of the central nervous system characterized by impairments in social interaction, communication and restricted repetitive and stereotyped behavior. It is generally assumed that in most cases autism has a polygenic cause, but the pathogenesis is still unknown. Neurobeachin (NBEA) has recently been identified as a candidate gene for autism in a patient with a de novo chromosomal translocation and three patients with a monoallelic deletion. This multidomain scaffolding protein has been suggested to be involved in neuronal post-Golgi membrane traffic. Knockout of Nbea in two independent mouse models has demonstrated a role in neurotransmitter release and synaptic functioning. Knockdown in a cell line has shown a role as negative regulator of secretion of large dense-core vesicles (LDCVs) and haploinsufficiency in blood platelets results in dense granules with an aberrant morphology. A potential role in vesicle transport is further supported by a study of SEL-2, the C.elegans homologue of NBEA. This protein was identified as a negative regulator of LIN-12/Notch activity, probably due to defects in endosomal trafficking. Members of the Notch pathway have also been shown to be modifiers of the NBEA homologue in Drosophila, rugose. These new insights in the function of NBEA may help identifying novel pathways affected in autistic patients. In particular, it suggests that impaired functionality of LDCVs, which contain neurotrophins, neuropeptides and monoamines, might contribute to the pathogenesis of autism in at least a subgroup of patients.

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Molecular genetic delineation of a deletion of chromosome 13q12→q13 in a patient with autism and auditory processing deficits

Cited by 47 publications

References 24 publications

Role of response gene to complement 32 in diseases

Role of response gene to complement 32 in diseases

Perinatal anoxia degrades auditory system function in rats

The Autism Candidate Gene Neurobeachin Encodes a Scaffolding Protein Implicated in Membrane Trafficking and Signaling

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