Biomedical subjects
Publications and source records attributed to J Lindsten.
Three families with infants affected with campomelic dysplasia, a genetically determined mesenchymal disease frequently associated with sex reversal were studied. Two XY females with ovarian gonadal differentiation and typical clinical features of campomelic dysplasia could be tested for H-Y antigen and were found to be H-Y negative.
Eleven patients with the so-called Cat Eye syndrome are reported including a more detailed description of the original cases reported by Schmid and Fraccaro. All cases had, in addition to a normal karyotype, a small extra G-like chromosome which appeared to be an isochromosome for the juxtacentromeric region (pter to q11) of an acrocentric chromosome. None were mosaics. Clinical findings and further cytogenetic studies in a few cases suggest that these markers probably derive from a No. 22 chromosome. Characteristic features of the Cat Eye syndrome in these 11 patients and those reviewed from the literature are: ocular coloboma which may involve the iris, choroid and/or optic nerve, preauricular skin tags and/or pits which are probably the most consistent feature, congenital heart defect, anal atresia with a fistula, renal malformations such as unilateral absence, unilateral or bilateral hypoplasia, and cystic dysplasia, and antimongoloid position of eyes. Intelligence is usually low-normal, although moderate retardation is also seen. There is great variability in the clinical findings ranging from near normal to lethal malformations. Less frequent, but also characteristic findings are: microphthalmia, microtia with atresia of the external auditory canal, intrahepatic or extrahepatic biliary atresia and malrotation of the gut. Direct transmission of the marker from one generation to the other was observed in both sexes. In those families, there was considerable variability in the clinical findings between affected family members. These cases show that there is a bias of ascertainment for patients who have the more striking malformations, especially those with ocular coloboma and anal atresia, a combination which appears to be present in only a minority of cases. Many mildly affected patients probably remain undetected. It is proposed that the term Cat Eye syndrome should be applied only to cases with trisomy or tetrasomy of not more than 22pter to q11 and without additional duplication or deletion of another autosomal segment.
Sixteen pregnancies at risk for Gaucher disease -- six with the Norrbottnian form, one with a juvenile form with a similar clinical course to the patients from Norrbotten and nine with the infantile from -- have been monitored by the assay of beta-glucosidase activity in cultivated amniotic fluid cells with natural labelled glycosylceramide as substrate. Two methods of cultivation were compared in respect of their effect on the activity of lysosomal enzymes. No significant difference was found between the two marker enzymes, beta-galactosidase and N-acetyl-beta-glucosaminidase, but the beta-glucosidase activity was significantly higher in the cells cultivated with one of the methods. In four of the pregnancies at risk, the beta-glucosidase activity in the cultivated amniotic fluid cells was less than 5% of that in the two control materials. These fetuses were regarded as affected with Gaucher disease and were aborted. Differentiation between controls and Gaucher heterozygotes was not possible in cultivated amniotic fluid cells. The diagnosis of Gaucher disease in the amniotic fluid cells was confirmed in three of the four cases by the assay of the beta-glucosidase activity in the liver nd brain of the aborted fetuses. The glucosylceramide content of the liver from two aborted fetuses was not augmented. The beta-glucosidase activity was examined in seven placentas from pregnancies at risk for Gaucher disease and found to be in agreement with that in the cultivated amniotic fluid cells.
Krabbe disease was diagnosed prenatally in Göteborg (Sweden) and Lyon (France) by assaying the cerebroside-beta-galactosidase activity with galactosylceramides and lactosylceramides as substrates in cultivated amniotic fluid cells. Altogether, 48 pregnancies at risk were monitored between 1972 and 1980. Ten pregnancies at risk were terminated because of a predicted affection of the fetus. Biochemical examination of material available from 7 of the 10 abortuses confirmed the diagnoses. All the remaining 36 pregnancies ended in the birth of a healthy infant. The study showed that prenatal diagnosis of Krabbe disease is difficult because of the relatively high residual cerebroside-beta-galactosidase activity in some affected fetuses. Except for the large biological variation, the enzyme activity was sensitive to variation in cultivation conditions and differed strikingly between morphologically different cell types. These two factors were controlled by including control cell samples cultivated under identical conditions and by relating the cerebroside-beta-galactosidase activity to that of two marker enzymes. The biological variation was investigated further by measuring the cerebroside-beta-galactosidase activity in cultured skin fibroblasts from infants with Krabbe disease and from their parents. Results obtained in 18 unrelated patients with Krabbe disease, 26 obligate heterozygotes and 63 controls showed a wide range of variation in enzyme activity in the controls, a large overlap between the controls and obligate heterozygotes, and a high residual activity in some patients. Nevertheless, a high residual activity in a patient was combined with a relatively high enzyme activity in the two parents. In the light of the above findings and deliberations, it appears warranted to conclude that laboratories with experienced personnel can make a reliable prenatal diagnosis of Krabbe disease and that the examination should be offered to all known couples at risk.
The incidence of Down's syndrome has been studied among children born in Sweden during the years 1968-1977. The risk for mothers of different ages of bearing such a child did not change during these years. This does not exclude that a change in incidence might have occurred in smaller areas of the country but escaped detection for statistical reasons. A higher than expected number of children with Down's syndrome were born in a few communities, which most likely is a chance event. No correlation could be detected between the incidence of Down's syndrome and a number of socioeconomic variables. The correlation with maternal age was studied in detail. There was a significant excess of males among both the newborn children with Down's syndrome and fetuses with trisomy 21 aborted after prenatal diagnosis. A similar tendency was found among the cases with a chromosome mosaicism but not among those with a translocation. Two hypotheses are put forward to explain the excess of males with trisomy 21.
The results of some family and experimental studies related to psoriasis are summarized. Complex segregation analysis of Lomholt's classical family material of psoriasis from the Faroe Islands gave clear evidence of a major locus (additive gene with a frequency of 0.07) plus a strong polygenic component (genetic heritability 0.87). An analysis of another family material showed complete linkage between the major locus for psoriasis and the HLA region. Treatment of cells with 8-methoxypsoralene plus a small dose of UVA induces monoadducts, some of which appear to remain in the DNA for at least 7 days of post-treatment incubation. These monoadducts can be activated to form DNA cross-links by a second, larger UVA dose. 8-Methoxypsoralene plus UVA-induced DNA cross-links can be modified by a repair process which involves the formation of DNA breaks. This process in not observed in XPA cells.
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Fibroblasts from 13 homozygotes and 27 obligate heterozygotes with the Norrbottnian type of Gaucher disease and 17 controls were cultivated and assayed with five beta-glucosidase methods, two with D-[glucose-U-14C] glucosylceramide and three with the artificial substrate 4-methylumbelliferyl-beta-glucoside. Two marker enzymes were assayed on the same cell samples, 4-methylumbelliferyl-beta-galactosidase and N-acetyl-beta-glucosaminidase. The beta-glucosidase activity of cultured fibroblasts, as measured with all five beta-glucosidase methods, was significantly lower (P < 0.001) for Gaucher homozygotes than heterozygotes. There was no overlap between fibroblasts from Gaucher homozygotes and the others with any of the beta-glucosidase methods used. The beta-glucosidase activity was also significantly lower (P < 0.001) for Gaucher heterozygotes than controls. However, none of the five beta-glucosidase assays differentiated between all Gaucher heterozygotes and controls, as several overlaps occurred in each assay.
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Apparently identical twin boys are both XX/XY and have two populations, A1 and B, of cells in their peripheral blood. Chimerism in somatic tissue outside the blood cells can be demonstrated in only one of the twins. From analysis of chromosomes and many gene markers the mechanism of origin of the unusual twins remains unclear.
Refractory hypochromic anemia was investigated in an adult with Turner's syndrome. Reduced iron absorption, serum iron, and iron incorporation were found in association with increased iron binding capacity and plasma iron turnover. 14 of 57 additional XO subjects were found anemic.
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A person with Turner's syndrome was described by Dr. Charles Pears in the Philosophical Transactions of the Royal Society, London, in 1805. The description included behavioral traits of mild temperament, absence of heterosexual interests, and concern about social stigmatization. These traits are the object of current behavior genetic studies of persons with Turner's syndrome.
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