Pathological Observations in Ataxia-Telangiectasia a Report on Five Cases

Aguilar, Mary Jane; Kamoshita, Shigehiko; Landing, Benjamin H.; Boder, Elena; Sedgwick, Robert P.

doi:10.1097/00005072-196810000-00009

Cited by 115 publications

(78 citation statements)

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“…Histopathological examination of this disease has already been made in detail by Aguilar et al (1968) , and concerning the central nervous system, almost the sane findings were noted in our case. The thymus weight was only 1/10 the normal weight of 25-35 g. Immunological deficiency accompanied by this disease can be quite a plausible explanation for high infectivity.…”

Section: Discussionsupporting

confidence: 71%

Stomach Cancer of a 14-Year-Old Boy with Ataxia-telangiectasia

Watanabe¹,

Hanazono²,

Sogawa³

et al. 1977

Tohoku J. Exp. Med.

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Section: Discussionsupporting

confidence: 71%

Stomach Cancer of a 14-Year-Old Boy with Ataxia-telangiectasia

Watanabe¹,

Hanazono²,

Sogawa³

et al. 1977

Tohoku J. Exp. Med.

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“…Peripheral neuron degeneration is undoubtedly present in our patients, convincing evidence of anterior horn cell degeneration, however, could not be shown. The latter is well-known to occur in neuropathological reports [17,24]. Taking into account the long survival of our patients such changes are likely to be present.…”

Section: Discussionmentioning

confidence: 54%

An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myclonia: a probable ataxia telangiectasia variant

Graaf

Jong

Kleijer

1995

Clinical Neurology and Neurosurgery

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We report a family of 4 siblings from a non-consanguineous marriage, presenting with an early onset recessive cerebellar ataxia and progressive distal limb wasting. Ocular or other telangiectasias were absent. There were neither frequent infections nor immunodeficiencies. The two youngest patients exhibited an incapacitating myoclonus which abated markedly after 20 years. Late onset diabetes was demonstrated in 3 patients. Hypogonadism was not a feature and there was a prolonged survival in the 4 patients. The oldest sibling died of a pancreatic adenocarcinoma, c~-Fetoprotein was elevated with normal carcinoembryonic antigen values in three patients. Cytogenetic analysis and radioresistant DNA synthesis was compatible with the diagnosis of ataxia-telangiectasia. This family probably represents a rare variant of ataxia-telangiectasia.

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“…Another ATM-targeted pig has recently been reported using similar strategy , however that model is still in early stages, and only the generation of heterozygote females was described without any neurological or behavioral characterization (66). The initial characterizations have shown several neuropathologic and motor features of AT patients (15,16,52,53) suggesting the suitability of the new model to study AT.…”

Section: Discussionmentioning

confidence: 99%

“…ATM is an ubiquitously expressed protein involved with many cellcycle checkpoints and functions as a DNA damage response protein (12,13) however, the underlying mechanism(s) linking ATM to neurodegeneration remain unclear. Postmortem brain specimens from AT patients have shown neurodegenerative features particularly localized in the cerebellum with extensive Purkinje cell (PC) and granule cell loss (14)(15)(16), but the events leading to this neurodegeneration and why ATM affects the cerebellum are unknown.…”

Section: Introductionmentioning

confidence: 99%

A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease

et al. 2015

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Ataxia telangiectasia (AT) is a progressive multisystem disorder caused by mutations in the AT-mutated (ATM) gene. AT is a neurodegenerative disease primarily characterized by cerebellar degeneration in children leading to motor impairment. The disease progresses with other clinical manifestations including oculocutaneous telangiectasia, immune disorders, increased susceptibly to cancer and respiratory infections. Although genetic investigations and physiological models have established the linkage of ATM with AT onset, the mechanisms linking ATM to neurodegeneration remain undetermined, hindering therapeutic development. Several murine models of AT have been successfully generated showing some of the clinical manifestations of the disease, however they do not fully recapitulate the hallmark neurological phenotype, thus highlighting the need for a more suitable animal model. We engineered a novel porcine model of AT to better phenocopy the disease and bridge the gap between human and current animal models. The initial characterization of AT pigs revealed early cerebellar lesions including loss of Purkinje cells (PCs) and altered cytoarchitecture suggesting a developmental etiology for AT and could advocate for early therapies for AT patients. In addition, similar to patients, AT pigs show growth retardation and develop motor deficit phenotypes. By using the porcine system to model human AT, we established the first animal model showing PC loss and motor features of the human disease. The novel AT pig provides new opportunities to unmask functions and roles of ATM in AT disease and in physiological conditions. † These authors contributed equally.

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Pathological Observations in Ataxia-Telangiectasia a Report on Five Cases

Cited by 115 publications

References 0 publications

Stomach Cancer of a 14-Year-Old Boy with Ataxia-telangiectasia

Stomach Cancer of a 14-Year-Old Boy with Ataxia-telangiectasia

An early-onset recessive cerebellar disorder with distal amyotrophy and, in two patients, gross myclonia: a probable ataxia telangiectasia variant

A novel porcine model of ataxia telangiectasia reproduces neurological features and motor deficits of human disease

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