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1. |
Prenatal diagnosis of Krabbe disease |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 79-89
Marie T. Vanier,
Lars Svennerholm,
Jan‐Eric Månsson,
Gunilla Hakansson,
André Bou,
Jan Lindsten,
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摘要:
Krabbe disease was diagnosed prenatally in Göteborg (Sweden) and Lyon (France) by assaying the cerebroside‐β‐galactosidase activity with galactosylceramides and lactosyl‐ceramides 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‐β‐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‐β‐galactosidase activity to that of two marker enzymes. The biological variation was investigated further by measuring the cerebroside‐β‐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
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01813.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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2. |
Genetics of the low density lipoprotein receptor: |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 90-103
Kjell Maartmann‐Moe,
Pal Berg‐Johnsen,
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摘要:
Six indices of low density lipoprotein (LDL) receptor activity were assayed in cultured fibroblasts from seven subjects with familial hypercholesterolemia (HC) and six subjects without HC (non‐HCs). Four non‐HCs, three HC heterozygotes and one HC homozygous proband belonged to one kindred (kindred A). The proband's fibroblast125I‐LDL processing values fell within or were slightly above the range defined by fibroblasts from three “receptor‐negative” HC homozygotes. Thus, the plasma membrane receptor defect in this kindred is probably of the “receptor‐negative” category.LDL receptor‐dependent125I‐LDL processing was about twice as high in fibroblasts from non‐HCs as in those from HC heterozygotes belonging to kindred A. The segregation pattern of LDL receptor activity in this kindred was compatible with control by a single gene locus.12SI‐LDL processing values from non‐HCs, HC heterozygotes and HC homozygotes differed significantly from one another, but non‐HCs and HC heterozygotes showed some overlap. LDL receptor‐dependent125I‐LDL association (plasma membrane binding plus intracellular accumulation) data for 6 HC heterozygous and 13 non‐HC fibroblast strains clustered into two and into three groups, respectively. Median125I‐LDL association levels in these groups appeared to be in agreement with the hypothesis that two different genotypes in HC heterozygotes and three in non‐HCs determined LDL receptor activity. These findings suggest the possibility that125I‐LDL processing studies may reveal
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01814.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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3. |
Genetics of the low density lipoprotein receptor: |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 104-112
Per Magnus,
Kjell Maartmann‐Moe,
Wendy Golden,
Walter E. Nance,
Kåre Berg,
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摘要:
Fibroblast low density lipoprotein (LDL) plasma membrane receptor activity, measured as 125I‐LDL association (plasma membrane binding plus intracellular accumulation) and degradation was determined in cell strains from 14 monozygotic (MZ) and 21 like‐sexed dizygotic (DZ) normolipidemic twin pairs. The twins were between 57 and 62 years old and had lived apart for an average of 38 years (range 0–60). The intrapair differences were significantly smaller in MZ than in DZ twin pairs in fibroblast 125I‐LDL association as well as degradation assays (P<0.05). These findings suggest a genetic influence on normal variation in LDL receptor activityin vitro.In two MZ pairs discordant for psoriasis, the psoriatic twin had markedly lower LDL receptor activity than the
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01815.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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4. |
Genetics of the low density lipoprotein receptor: |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 113-129
Kjell Maartmann‐Moe,
Per Magnus,
Wendy Golden,
Kåre Berg,
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摘要:
Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I‐LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non‐HCs) were tested for 125I‐LDL association and degradation. Both LDL receptor activity indices were twice as high in non‐HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non‐HC and HC heterozygous values was found in the 125I‐LDL association assay [median (range) 970 (330–2500), and 450 (250–940), respectively] and in the degradation assay [median (range) 810 (280–2020), and 470 (160–790), respectively]. The values are expressed as ng125I‐LDL mg cell protein‐14.5 h‐1.These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination.The LDL receptor‐dependent125I‐LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01816.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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5. |
Partial trisomy 3q due to a de novo translocation t(X;3) (p21;q12) |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 130-134
J. W. E. OORTHUYS,
R. M. SLATER,
H. BARROWCLOUGH,
M. J. K. DE KLEINE,
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摘要:
A patient with several congenital malformations, principally in the face, cardiovascular system and genitalia, was found to have the karyotype46,X,der(X),t,X;3)(Xqter← p21::3ql2‐←3qter). A comparison of the clinical and cytogenetical findings with similar cases in the literature led to the conclusion that a partial trisomy 3q is the most likely cause for the symptoms in this pa
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01817.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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6. |
Carrier detection in Sanfilippo syndrome type B: report of six families |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 135-140
J. M. Vance,
P. M. Conneally,
R. S. Wappner,
P. L. Yu,
I. K. Brandt,
M. A. Pericak‐Vance,
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摘要:
Serum samples from 175 individuals in six Sanfilippo syndrome type B (SFB) families and 360 White controls were assayed for serum α‐N‐acetyl‐D‐glucosaminidase (NAG) activity. Only minimal overlap was observed between the controls' NAG activity distribution and that of the 12 obligate heterozygotes. The distribution of NAG activity was log transformed to reduce skewness, and segregation of family members with a prior risk of being a SFB carrier was well within expected limits. However, in one consanguineous family the NAG activity of both parents of one SFB obligate heterozygote was within the normal range for NAG activity. Plausible explanations for this finding are discussed. Additionally, the serum NAG activity of one control and her mother were found to lie within one standard deviation of the obligate heterozygote mean. These individuals are most probably carriers
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01818.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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7. |
Development of eight pubertal males with 47,XXY karyotype |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 141-146
James A. Salbenblatt,
Bruce G. Bender,
Mary H. Puck,
Arthur Robinson,
M. Lynn Webber,
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摘要:
The increasing frequency with which the diagnosis of the 47,XXY karyotype is made requires more knowledge of the prognosis of this condition. We present four 47, XXY boys identified at birth and followed since then (Group I), and four 47, XXY boys diagnosed because of physical and/or emotional problems (Group II). Physical, psychological, language, and hormone data are presented. The physical and intellectual profiles for the two groups are similar. This is in contrast to the very poor school and emotional adjustment of the Group II individuals. These boys were definitely more difficult and problematic for their parents when compared to their siblings and to Group I who were un‐selected. This further emphasizes that the expression of this karyotype is variable and individuals with behavioral disorders may represent a maladaptive subgroup rather than the entire population of 47,XXY males. Recommendations are given for intervention with attention to learning and language problems, hormone status, and emotional stat
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01819.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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8. |
Complex segregation analysis of the Lp(a)/pre‐ß1‐lipoprotein trait |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 147-151
L. Iselius,
G. Dahlén,
U. DE Faire,
T. Lundman,
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摘要:
Complex segregation analysis of the LpCaypre‐β1‐lipoprotein trait in 229 nuclear families gave strong evidence for a major gene with complete dominance for pre‐β+and gene frequency q = 0.10. The penetrance is 0.917. There was no evidence for either polygenic heritability or environment common
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01820.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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9. |
Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B, and C) |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 152-160
J. J. P. VAN DE Kamp,
M. F. Niermeijer,
K. VON Figura,
M. A. H. Giesberts,
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摘要:
A study of 73 patients with the Sanfilippo syndrome (36 patients with Sanfilippo A disease, 23 with Sanfilippo B disease and 14 with Sanfilippo C disease) revealed both intertype and intratype variability. The course of the disease was relatively mild in Sanfilippo B disease and dementia was less severe. Type A showed earlier onset with more severe clinical manifestations and an earlier age at death. Sanfilippo C disease was slightly less severe than Sanfilippo A disease. The intratype variability may be explained in part by differences in genetic and environmental background. In Sanfilippo B disease, genetic heterogeneity is suggested by the observation of a more severe and a mild variant, and this variation may be due to the involvement of different allelic mutations. The intra‐familial variability of the different types was small, but in three families with Sanfilippo B disease intrafamilial variability was eviden
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01821.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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10. |
Multiple forms of membrane‐bound β‐glucosidase in Gaucher's disease |
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Clinical Genetics,
Volume 20,
Issue 2,
1981,
Page 161-167
MOHAMMED YAQOOB,
MARK CARROLL,
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摘要:
Two forms of membrane‐bound β‐glucosidase in the spleen of normal individuals were distinguished by their thermostability properties. The heat‐labile form A predominates; it catalyzes the hydrolysis of the natural substrate, glucosylceramide, and is activated by the detergent, sodium taurocholate. The minor heat‐stable form B is inactive against glucosylceramide and is inhibited by taurocholate. The activity of form A increases from childhood to adult life, as does the activity of the soluble β‐glucosidase and of glucosylceramide β‐glucosidase. In the spleen of nine patients with different types of Gaucher's disease the residual membrane‐bound β‐glucosidase was predominantly heat‐stable and inhibited by taurocholate. There was no clear correlation between the properties of the residual enzyme in the different types of the disorder and their respective clinical severity. The results are discussed in relation to the biochemical pathogenesis and the enzymatic diagnosis
ISSN:0009-9163
DOI:10.1111/j.1399-0004.1981.tb01822.x
出版商:Blackwell Publishing Ltd
年代:1981
数据来源: WILEY
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