Utilization of Electron Microscopy in the Prenatal Diagnosis of Genetic Disease

Wyatt, Philip; Cox, David

doi:10.1159/000152849

Cited by 9 publications

(4 citation statements)

References 20 publications

(26 reference statements)

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“…1 In addition, histological and clinical studies suggest that some of these patients have focal LV fibrosis. [2][3][4][5] Despite normal global LV function, regional myocardial function is impaired in both male and female patients and many patients die from heart failure. 1,6,7 Thus, using conventional echocardiography it is challenging to recognize the cardiac involvement of the disease.…”

Section: Introductionmentioning

confidence: 99%

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease

Weidemann¹,

Breunig²,

Beer³

et al. 2005

European Heart Journal

210

149

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Section: Introductionmentioning

confidence: 99%

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease

Weidemann¹,

Breunig²,

Beer³

et al. 2005

European Heart Journal

210

149

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“…One of the parameters to be considered is the day of harvest, as this was shown to have an effect on skin fibroblasts (Comings and Okada, 1970;Lucky et al, 1975). The protocol in a number of studies entails removing the cells 4-5 days after subculture (Ornoy et al, 1978;Wyatt and Cox, 1977). Our EM results indicate that cultures can be examined till the 10th day after subculture.…”

Section: Discussionmentioning

confidence: 91%

Cultured amniotic fluid cells for prenatal diagnosis of lysosomal storage disorders: A methodological study

Arnon

Ornoy

Bach³

1986

Prenatal Diagnosis

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The influence of culture conditions on the ultrastructure and enzyme activities of amniotic fluid cells are reported. Morphological changes were determined as a function of the number of lysosomal-like inclusion bodies per cell, and these results correlated to the activity of beta-hexosaminidase, alpha-mannosidase, beta-glucuronidase, arylsulphatase C and 5' nucleotidase. The parameters examined were pH of the culture media, type of media, increasing cell passage and day of harvest. Our results indicate that enzyme activities are less sensitive to changes in culture conditions as compared to ultrastructural changes. We therefore recommend that in order to obtain reliable ultrastructural results for the diagnosis of storage disorders, cultures should be grown in MEM as the culture medium, the pH of the medium carefully monitored to remain below pH 7.4, examining the cultures no later than the eighth cell passage and no later than the 10th day after subculture.

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“…First, it provides a second method for confirmation of the disease, thus complementing current biochemical methods of diagnosis. The relevance of this in the developing field of prenatal diagnosis has been recently described (18). Second, it may prove to be of value in the possible development of enzyme replacement therapy.…”

Section: Discussionmentioning

confidence: 96%

Tay-Sachs Disease: Ultrastructural Studies on Cultured Fibroblasts

1978

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SummaryThe knowledge that the biochemical lesion associated with Tay-Sachs disease is demonstrable in many tissues, and in particular in cultured fibroblasts, suggested that ultrastructural lesions might also accompany hexosaminidase A deficiency in cultured fibroblasts. Electron microscopic studies on six human skin fibroblast lines and four amniotic fluid fibroblast lines, biochemically confumed to be deficient in hexosaminidase A, showed characteristic cvtoplasmic inclusions not observed in any normal lines studied. u p i o 60 of these abnormal cytoplasm^ inclusions were observed in full cell cross sections in all affected lines examined. SpeculationElectron microscopy of cultured fibroblasts deficient in hexosaminidase A may have value in the understanding of the cellular processes which led to Tay-Sachs disease. Ultrastructural examination may also prove to be of value in the prenatal diagnosis of the disease and possible enzyme replacement therapy Tay-Sachs disease, also termed Gm, gangliosidosis type I, is an autosomal recessive condition which is found predominantly among decendants of Ashkenazie Jews (1 1). The frequency of carriers in these populations is approximately 1 in 30 and the frequency of affected individuals approximately 1 in 4000 live births in this ethnic group (16). Individuals affected with TaySachs disease usually die by 5 years of age.The biochemical abnormality in this disease has been determined to be a marked deficiency in the enzyme hexosaminidase A which, because of the altered metabolic activity, leads to the accumulation of ganglioside Gm, in numerous tissues of the affected individual (13). The accumulation of ganglioside Gm, has also been detected in cultured cells (2). Biochemical assay of the activity of hexosaminidase A has been determined in liver, brain, skin, kidney, leukocytes, serum, cultured fibroblasts, and amniotic fluid cells (6, 13). In addition, electron microscopic examination of neuronal cells from children affected with Tay-Sachs disease has shown the presence of numerous membraneous cytoplasmic bodies which are composed of concentrically arranged membranes, closely packed together (16). Some investigators consider these inclusions to be characteristic for the disease (12). The bodies measure between 0.5 and 2.0 p m in diameter and have been demonstrated to be the site of acid phosphatase activity, indicating their probable lysosomal origin (17). Chemical analysis demonstrates that they contain large quantities of ganglioside Gm, (15).The knowledge that the biochemical lesion associated with Tay-Sachs disease is demonstrable in many tissues and, in particular, in cultured fibroblasts, suggested that ultrastructural lesions might also accompany hexosaminidase A deficiency in cultured fibroblasts. To investigate this possibility, an electron microscopic examination was made of cultured cells known to be deficient in hexosaminidase A .We have demonstrated that cultured fibroblasts derived from individuals affected with Tay-Sachs disease have distinct morphologic ...

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Utilization of Electron Microscopy in the Prenatal Diagnosis of Genetic Disease

Cited by 9 publications

References 20 publications

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease

Cultured amniotic fluid cells for prenatal diagnosis of lysosomal storage disorders: A methodological study

Tay-Sachs Disease: Ultrastructural Studies on Cultured Fibroblasts

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