Conflicting reports of imprinting status of human GRB10 in developing brain: how reliable are somatic cell hybrids for predicting allelic origin of expression?
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Alleles↗
Biomedical subjects
H H Ropers
Publications and source records attributed to H H Ropers.
Progressive myoclonus epilepsy. A variant with probable X-linked inheritance.
The syndrome of myoclonus, epilepsy, and mental deficiency is observed in a number of distinct nosologic entities differing with respect to clinical course, (--) pathologic, and biochemical findings. Genetically, the heterogeneity within this group of disorders is shown by the occurrence of autosomal recessive and dominant forms with incomplete penetrance. In this paper we report on a sibship with at least four affected males suffering from progressive myoclonus epilepsy, ataxia, and mental deterioration. The syndrome is probably X-linked, as suggested by the maternal transmission and mild, variable symptoms in some female carriers. In a survey of the literature we have found another pedigree suggesting X-linked inheritance of this variant of progressive myoclonus epilepsy.
Adult↗
Periodic hypokalemic paralysis transmitted by an unaffected male with negative family history: a delayed mutation?
A pedigree is described that includes three cases of periodic hypokalemic paralysis. Apparently, the disease has arisen by de novo mutation in a father of two affected daughters, who, however, is not affected himself. This is unexpected, since in males the disorder is generally inherited as a fully dominant trait. Therefore we propose that these findings result from an early somatic or a half-chromatid mutation.
Adolescent↗
Clinical and biochemical investigations on patients with partial deficiency of placental steroid sulfatase.
We report on three independent cases with a partial deficiency of placental steroid sulfatase (E.C.3.1.6.2). Upon routine pregnancy monitoring these patients were detected on the basis of low estriol excretion and failing induction of labor. In all three cases a male was delivered and subsequently the diagnosis of partial deficiency of placental steroid sulfatase was confirmed enzymatically in placenta homogenates. In one case, fibroblast cultures were established from skin explants of mother and son. In fibroblasts of the child, as in placental tissue, the activity of steroid sulfatase was only 34% of normal. Similar values were obtained for arylsulfatase C, though this enzyme is clearly separable from steroid sulfatase by electrophoresis. In cells of the mother, enzyme activities were unremarkable.
Arylsulfatases↗
Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals?
In placenta membranes of newborn girls carrying electrophoretically distinguishable G6PD alleles, the maternally derived isozyme is expressed preferentially. This phenomenon cannot be explained by allelic differences in enzyme activity or by somatic selection directed against cells with particular G6PD phenotypes. Instead, it may be that in this tissue X inactivation is nonrandom. Preferential expression of the maternal X chromosome, as has been shown in marsupials and in extraembryonic membranes of rodents and now in man, may reflect the state of activity of the X chromosomes in the early stages of female embryonic development.
Female↗
Distribution of G6PD phenotypes in red blood cells of Southern African Negroids: evidence for somatic selection.
In a recent population study, we observed a striking deficit of G6PD heterozygotes among Southern African Negroid females. This finding was interpreted tentatively as evidence for a small number of hematopoetic stem cells in man. In a follow-up study we examined peripheral blood and cord blood in 547 mothers and in their newborn offspring. In mothers and sons, the frequencies of the G6PD alleles are apparently quite different. When the allele frequencies determined in sons are used for calculation of the expected phenotype frequencies in mothers and daughters, there is a large deficit of maternal G6PD AB phenotypes, and an equivalent surplus of G6PD homozygotes. However, no relevant heterozygote deficit is observed in newborn daughters. This discrepancy may be explained by the assumption that in peripheral blood of heterozygotes carrying the GdA- allele, G6PD-deficient cells progressively become eliminated during development from birth to adulthood. In other words, the large heterozygote deficit observed in adult females may be due to somatic selection rather than to a small pool of hematopoetic cells at the time of X differentiation.
Alleles↗
On the incidence of unilateral and bilateral colour blindness in heterozygous females.
In 303 mothers of colour-blind sons, both eyes were tested with pseudoisochromatic plates and with the anomaloscope. Two hundred thirty healthy normal and 56 colour-blind males served as controls. In good agreement with the expected proportion of homozygotes in our sample, 17 colour-blind mothers were detected. Eight others had difficulty reading pseudoisochromatic plates and were conspicuous at the anomaloscope. In these, both eyes were affected to a very similar, moderate degree. Monocular disturbances of colour vision were not observed in the entire series. Our data suggest that (1) in most (if not all) of the carriers with colour vision impairment, there is no complete lack of normal retina cones, and (2) the proportion of defective retina cones is remarkably similar in both eyes of individual heterozygotes. The latter observation may indicate that at the time of X-differentiation there is a common primordial cell pool for both retinas.
Adolescent↗
X-linked mental retardation: transmission of the trait by an apparently unaffected male.
A pedigree is presented in which an apparently unaffected man transmitted the gene for X-linked mental retardation to at least four of his 12 daughters. None of his 12 sons was mentally retarded. These findings may be explained by a somatic mutation and germinal mosaicism in the father or by a half chromatid mutation in maternal gametes.
Adult↗
Assignment of the gene for human glucose dehydrogenase (E.C. 1.1.1.47) to chromosome 1 using somatic cell hybrids.
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Animals↗
Variable composition of X chromosomal mosaics: due to asynchronous cell division during early embryogenesis?
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Animals↗
Tentative evidence for 3--4 haematopoetic stem cells in man.
Blood specimens from a random sample of 981 South African Negroid females were typed electrophoretically inter alia for their G-6-PD phenotypes, The allele frequency for GdB and GdnonB was found to be 0.8126 and 0.1874 respectively. Calculating the number of individuals expected for each phenotypic class, a highly significant deviation from the Hardy-Weinberg equilibrium became manifest, i.e. there was a deficit of 24.6% of heterozygotes and an excess of 12.3% of each of the two classes of homozygotes. Several possible reasons for this discrepancy e.g. the effects of pooling sub-samples, selection and misclassifications due to insufficient staining were examined and were found not be likely explanations for the observed phenomenon. Instead, the result is interpreted as due to only 3--4 stem cells which give rise to the haematopoetic system in man.
Cell Differentiation↗
Adrenoleukodystrophy (Siemerling-creutzfeldt disease): Heterozygote with two clonal fibroblast populations.
On the fifth day after subcultivation,, fibroblasts of two unrelated patients with adrenoleukodystrophy (Siemerling-Creutzfeldt disease (SCD)) developed typical morphologic anomalies which could be seen by light microscopy. From skin biopsy material of an obligatorily heterozygous womam, both normal and morphologically defective colonies could be isolated. These findings suggest that the morphologic alterations are an expression of the defect in Siemerling-Creutzfeldt disease. Futhermore, they suggest that the SCD locus is subject to lyonization.
Adrenal Cortex Diseases↗
Evidence for preferential X-chromosome inactivation in a family with Fabry disease.
Severe clinical signs of Fabry disease were observed in four of eight heterozygous daughters of a male patient. Activities of alpha-galactosidase A in serum, white blood cells, and hair roots of the manifesting carriers were markedly lower than 50% of normal. These findings are not easy to interpret in terms of random X inactivation alone; several alternative models including nonrandom (preferential) X inactivation are discussed.
Blood Group Antigens↗
Fabry's disease: heterozygote detection by hair root analysis.
Fabry's disease (angiokeratoma corporis diffusum) can be diagnosed by determination of alpha-galactosidase activity in single hair roots. A technique has been developed permitting subsequent analysis of enzyme activity and protein content of hair root cells. We have applied this method examining 8 obligatorily heterozygous sisters as well as their 5 daughters and 10 sons. Especially for identification of heterozygotes, the method described proved to be easy and reliable.
Clinical Enzyme Tests↗
Prenatal diagnosis of homoxygous familial hypercholesterolemia: investigation of a case at risk.
Cultivated amnion cells obtained from a pregnancy at risk for the homozygous form of familial hypercholesterolemia were analyzed, as were fibroblasts from normal, heterozygous and homozygous controls. Three different methods were employed in order to compare their diagnostic value: i. Acetate incorporation into the cellular 3beta-OH-sterol fraction; ii. LDL-binding to the cell surface receptor; and iii. Oleate incorporation into the cholesterylester pool of the cells after addition of LDL to lipoprotein-deficient growth medium. The best discrimination between normal, heterozygous and homozygous cells was achieved using the third technique. On the basis of the acetate incorporation analysis, we concluded that the child is not homozygous, but probably completely unaffected. This diagnosis was confirmed by repeated determinations of plasma cholesterol levels during the first 11 months of life. Our investigations further substantiate the specularion that prenatal diagnosis of this disorder is possible.
Acetates↗
Complementation after fusion of Sandhoff- and Tay-Sachs fibroblasts.
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Cell Fusion↗
Leukodystrophy, skin hyperpigmentation, and adrenal atrophy: Siemerling-Creutzfeldt disease. Transmission through several generations in two families.
Two apparently unrelated families with a history of leukodystrophy associated with adrenal insufficiency are presented. Only about 20 cases of this syndrome have been reported until now. It was first described by Siemerling and Creutzfeldt; therefore we propose the designation Siemerling-Creutzfeldt disease. Our pedigrees include 15 additional cases and prove that this disease is inherited as an X-linked or as an autosomal dominant trait with male sex limitation. Within these families, the interindividual variability of clinical signs is remarkable. Patients can survive into the fifth decade, and one has reproduced. Attempts to identify heterozygotes on the basis of endocrinologic investigations were unsuccessful.
Adrenal Cortex Hormones↗