bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of the low density lipoprotein receptor:
Authors: Maartmann‐Moe Kjell , Magnus Per , Golden Wendy , Berg Kåre 
Published: July 2010

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 ng 125I‐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‐dependent 125I‐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 to atherosclerosis in non‐HCs.
45 XO/49 XYYYY Mosaicism in a male with stigmata of Turner's syndrome
Authors: Pincheira Juana V. , Bustos‐Obregón Eduardo , Pumarino Hugo , Santos Manuel A. 
Published: July 2010

A male subject with Turner‐like stigmata and chromosomic constitution 45, XO (97.5%) and 49.XYYYY (1.1%) is reported.The finding of a low percentage line bearing Y chromosome in a patient with clinical features similar to those described for XO males, would support the hypothesis that masculinization in certain individuals with 45, XO karyotype may be due to an undetected mosaicism.
Cytogentic studies of a patient with mosaicism of isochromosome 13q and a dicentric (Y; 13) translocation showing differential centromeric activity
Authors: Ing Paul S. , Smith Shelley D. 
Published: July 2010

A case is presened in which both an isochromosome and a dicentric translocation with differential centromere activity are found in one individual. Three karyotypes are present: 46, XY, ‐13, isochromosome 13q is found in 23% of cells in blood and 5% in skin. The dicentric (Y;13), + i(13q)/45,X, ‐13, + psu dic(13)t(13;Y)/45,X, ‐13, + psu dic(Y)t(Y;13). The isochromosome in all of the remaining cells displays differential centromeric activity; the ratio of cells with the acitve 13 centromere to the acstive Y centromere is about 3.5:1.The formation of the isochromosome 13q was a de novo gametic event. The translocation producing the dicentric occurred after fertilization with the breakpoints at band Yq12 and the juxta‐centromeric region of the isochromosome 13. The finding of differential centromeric activity in this chromosome indicates that centromere inactivation is not always permanent in a dicentric translocation.
Marker chromosomes in parents to children with Down's syndrome
Authors: Annerén G. , Wahlström J. , Tommerup N. 
Published: July 2010

The incidence of an extra marker chromosome in the normal population is low, about 0.26 per 1,000, and that of trisomy 21 is about 1.25 per 1,000. The incidence of both these chromosomal abnormalities in the same family should be very low, if this occurs by chance.Thirteen cases of Down's syndrome in 10 families in which one of the parents had an extra marker chromosome have been reported earlier. In three of these families there were two siblings with Down's syndrome.The present report describes two families in which an extra marker chromosome was found in one of the parents and in which three of the offspring had a trisomy 21 karyotype. From the findings at Q‐ and AgNOR banding of the chromosomes it seemed probable that in one case this extra marker chromosome was an isochromosome for the short arm of an acrocentric chromosome.It seems very likely that marker chromosomes in healthy mothers are of pathogenetic importance for non‐disjunction, resulting in a trisomy 21 offspring. A finding of an extra marker chromosome in one of the parents should therefore be taken into consideration in genetic counselling.
The syndromic status of sclerosteosis and van Buchem disease
Authors: Beighton P. , Barnard A. , Hamersma H. , Wouden A. van der 
Published: July 2010

We have examined 50 persons with sclerosteosis in the Afrikaner community of South Africa and 15 individuals with van Buchem disease in Holland. The clinical and radiographic manifestations of these conditions are very similar, the only notable differences being greater severity and syndactyly in the majority of the patients with sclerosteosis.The Afrikaners have Dutch antecedants and it seems likely that these autosomal recessive disorders result from homozygosity of the same faulty genes. The phenotypic variation may be due to the epistatic effect of modifying genes in the Afrikaner population.
Dermal changes in Ehlers‐Danlos syndrome
Authors: Kobayasi Takasi , Oguchi Motoi , Asboe‐Hansen Gustav 
Published: July 2010

Skin biopsies from thirteen patients suffering from Ehlers‐Danlos syndrome, including 6 of the mitis type, 4 of the benign hypermobile type, one of the X‐linked type, one of the ocular type and one of the periodontitis type, were studied by electron microscopy after routine preparation.Collagen fibrils showed a distorted arrangement of bent, curled or twisted fibrils and threadlike material. Similar changes may be seen in the skin of other hereditary disorders of connective tissue. However, abnormal collagen fibrils in normal skin suggests one of eight Jypes of Ehlers‐Danlos syndrome. Clinical variants cannot be differentiated on the basis of ultrastructural findings. Elastic fibres were normal without degenerative changes. Perineurium was lacking in dermal nerves of most patients. Fibroblast‐like cells showed no cystic cisterna of endoplasmic reticula.
Cluster of acute infantile spinal muscular atrophy (Werdnig‐Hoffmann disease) in a limited area of Reunion Island
Authors: P<sc>ascalet‐Guidon Marie‐Josée , Bois Etienne , Feingold Josué , Mattei Jean‐François , Combes Jean‐Claude , Hamon Christine 
Published: July 2010

A retrospective study of Werdnig‐Hoffmann disease (spinal muscular atrophy type 1) was undertaken on Reunion Island. Nineteen WH cases born between 1969 and 1980 were recorded belonging to thirteen sibships of the European population of the island.Genealogical analysis, going back to the XVIIth century (1642), showed a relationship among the 13 families, which were derived from a common ancestral pair.A founder effect is the most probable explanation for the concentration of Werdnig‐Hoffmann disease in the area.
Mental retardation, short stature, minor skeletal anomalies, craniofacial dysmorphism and macrodontia in two sisters and their mother
Authors: Fryns J. P. , Haspeslagh M. 
Published: July 2010

Mental retardation associated with short stature, craniofacial dysmorphism, macrodontia and minor skeletal anomalies is reported in two sisters and their mother.The similarity with and the relationship to the KBG syndrome is discussed and the importance of clinical syndrome identification in familial mental retardation is emphasised.
Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease
Authors: Ginsberg Henry , Grabowski Gregory A. , Gibson Joyce Corey , Fagerstrom Richard , Goldblatt Jack , Gilbert Harriet S. , Desnick Robert J. 
Published: July 2010

Plasma lipid and serum apoprotein concentrations were determined in twenty‐nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein‐B and apoprotein‐AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein‐E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.This work was supported by the following grants: USPHS HL 23077, HD 07105, HL 25752, CA 31656 and RR‐71 from the National Institutes of Health; 1–273 and 1–578 from the March of Dimes Birth Defects Foundation; grant from the New York Heart Assocation. Dr. Ginsberg is a recipient of a Research Career Development Award HL 00949 and is an Irma T. Hirschl Career Scientist. Dr. Grabowski is a recipient of a Clinical Investigator Award HD 00386.
Combined sialidase (neuraminidase) and β‐galactosidase deficiency. Clinical, morphological and enzymological observations in a patient
Authors: Loonen M. C. B. , Reuser A. J. J. , Visser P. , Arts W. F. M. 
Published: July 2010

A patient with combined deficiency of sialidase and β‐galactosidase is described. This now 39‐year‐old man, who is of Japanese origin, showed gradually progressive clinical features from the age of six years. Many of these features are commonly found in sialidosis type 2 or in GM1‐gangliosidosis. Both sialidase and β‐galactosidase activities were deficient in leucocytes and cultured fibroblasts. Leucocytes of his mother showed activities of both enzymes in the lower limit of the control range.Morphologically, the pattern of storage products in a skin biopsy resembled in many respects that seen in GM1‐gangliosidosis. Moreover, storage products which could be typical of sialidosis were also observed. Since the patient showed angiokeratomata, the morphological findings were compared with those specific to Fabry's disease, but no similarities were found.An enzymological diagnosis of the disease is most reliable on cultured fibroblasts, discriminating it from sialidosis type 2 and GM1‐gangliosidosis. In view of recent findings, leucocytes seem to be less suitable for the establishment of the diagnosis galactosialidosis.
Diagnosing of chromosome abnormalities in Denmark
Authors: Nielsen J. , Videbech P. 
Published: July 2010

A survey of how frequent chromosome abnormalities are diagnosed in Denmark prenatally as well as postnatally compared with the expected incidence in an 11‐year period 1970–1980 has been made from the Danish Cytogenetic Central Register.Ten percent of the expected number of Klinefelter's syndrome, 41% of Turner's syndrome and 10% of other sex chromosome abnormalities in children born between 1970 and 1980 have been diagnosed until January 1, 1983.The total frequency of diagnosed cases with sex chromosome abnormalities is 13% of the expected number. Induced abortion was made in 62% of the cases with sex chromosome abnormalities diagnosed prenatally.Ninety percent of all cases with Down's syndrome were diagnosed by chromosome examination, and 10% were diagnosed prenatally and aborted. During the last part of the period from 1977–1980 this had increased to 20%. Thirty‐seven percent of cases with other chromosome abnormalities were diagnosed.Among the expected 4,396 children with chromosome abnormalities to be born between 1970 and 1980, a total of 39% were diagnosed postnatally until January 1, 1983, and 10% were diagnosed prenatally.It is concluded that there is a great need for training consultants in clinical genetics, expansion and further decentralization of cytogenetic service with more cytogenetic laboratories and employment of clinical geneticists in all 14 Danish counties.
Fetal mortality in sibships of cases with neural tube defects
Authors: Lippman Abby 
Published: July 2010

It has been suggested that rates of fetal mortality in sibships of probands with a malformation inherited as a multifactorial threshold trait may reflect their liability to the malformation. If so, spontaneous abortion rates should be more frequent in sibships thought to have greater liability. For anencephaly and spina bifida (ASB), then, spontaneous abortion should be higher in the sibships of male probands and in families with more than one affected case (multiplex families).This hypothesis was tested using data on cases from The Montreal Children's Hospital and from the literature. Approximately 5000 pregnancies were analyzed. Rates of abortion did not vary with the sex or diagnosis of the proband. The spontaneous abortion rate was slightly higher in multiplex than in simplex families, but the difference was not statistically significant and most likely reflects the differing reproductive patterns in the two types of families. Thus, if male probands and multiplex sibships do have, on average, more liability for ASB, this liability cannot be detected in spontaneous abortion rates in the sibships available for this analysis.
Low density lipoprotein receptors in cultured skin fibroblasts from psoriasis patients
Authors: Leren Trond P. , Maartmann‐Moe Kjell , Thune Per , Berg Kåre 
Published: July 2010

Low density lipoprotein (LDL) receptor activity, measured as 125I‐LDL association and degradation at 37 °C, was determined in cultured fibroblasts from involved as well as uninvolved skin obtained from 20 psoriasis patients. The same analyses were conducted in fibroblasts from two reference groups consisting of 19 heterozygotes for familial hypercholesterolemia and 16 normal subjects, respectively.Psoriasis patients had significantly lower LDL receptor activity than normals, and it was comparable to that of the heterozygotes for familial hypercholesterolemia. The reduced LDL receptor activity was not accompanied by an increase in total serum cholesterol. The psoriasis patients had a significant reduction in apo‐B concentration, but did not differ from the normals in the other serum lipid or lipoprotein parameters. There was no difference in LDL receptor activity between involved and uninvolved skin from psoriasis patients.These results suggest that there is an abnormal cell membrane in dermal fibroblasts from psoriasis patients. Since their total serum cholesterol is normal, their low LDL receptor activity may be confined to dermal cells, leaving the hepatic lipid metabolism normal. The pathogenetic significance of this finding is unknown.
Fetal mortality in oral cleft families (V): studies of sporadic vs familial and pure vs syndromic clefts
Authors: Dronamraju Krishna R. , Bixler David 
Published: July 2010

The frequencies of fetal deaths in sibships of oral cleft probands are analysed in relation to sporadic or familial clefts, and pure or syndromic clefts. In a study of 1823 pregnancies in 630 sibships of probands with CL(P), the frequency of fetal deaths was found to be increased, but not significantly, in the sporadic group as compared to the familial group of sibships from Indiana. However, such an increase was found to be significant in the Montreal data. The pooled data from both these centers also show a significant increase in the sporadic group. For CP, no such differences were found.Similar comparisons of fetal mortality in relation to pure and syndromic clefts indicated that the frequencies of fetal deaths were consistently elevated in sibships of probands with syndromic clefts with one exception, which is the Indiana CP group where the lowest frequency of fetal deaths was observed in the sibships. This group mostly consisted of sibships with solitary pregnancies. This may have been a result of early zygotic mortality in this group. Further data will be obtained to confirm this observation.
Biochemical studies in Niemann‐Pick disease. III: In vitro and in vivo assays of sphingomyelin degradation in cultured skin fibroblasts and amniotic fluid cells for the diagnosis of the various forms of the disease
Authors: Vanier Marie T. , Rousson Robert , Garcia Isabelle , Bailloud Geneviève , Juge Marie‐Christine , Revol A. , Louisot P. 
Published: July 2010

Sphingomyelinase activities were assayed in vitro in cultured skin fibroblasts of 61 patients with Niemann‐Pick disease (NPD). Residual activities found in type A and B were 1% and 4%, respectively, of the mean control values, i.e. significantly higher in type B. In 27 cases with NPD type C, the mean activity was 42% of that in controls, with residual activities ranging from 15% up to normal. Fifteen pregnancies at risk for NPD type A and B were monitored; 4 affected foetuses were found.The uptake of exogeneously added radiolabeled sphingomyelin by cultured cells and metabolism of the choline moiety of this lipid were studied in 35 patients with NPD and 14 controls. No difference of uptake between normal and mutant cells was observed. Normally, 77 ± 5% of the radioactivity taken up was converted to phosphatidylcholine after 18 h incubation, compared to 5±2% (n = 7) in NPD type A. A substantially greater hydrolysis (31 ±12%; n = 8) occurred in NPD type B, and the test allowed complete discrimination between these two types. In NPD type C, 16 patients showed an abnormally low rate of intracellular sphingomyelin degradation (48 ± 5%) while 4 others were not distinguishable from controls. There was a correlation (r = 0.76) between the results of the in vitro and in vivo assays, but also between the severity of the clinical symptoms and the impairment in sphingomyelin degradation. For the diagnosis of NPD type C, the in vivo test gave more reproducible and more clearcut results than the in vitro assay.
Dermatoglyphic findings in patients with fragile X‐chromosome
Authors: Hirth L. , Singh S. , Schilling S. , Müller E. , Goedde H. W. 
Published: July 2010

Finger‐ and palmar prints of hemi‐ and heterozygote fragile X‐patients with mental retardation (10 males and 5 females) were compared to dermatoglyphic findings in 20 mentally retarded patients (10 males and 10 females) without fragile X and to 200 healthy unrelated persons (100 males and 100 females).Characteristic whorls and double‐loops with high ridge‐counts on finger‐tips and a pronounced transversal course of palmar ridges were restricted to males with fragile X. Female carriers of fragile X showed, corresponding to male patients, some abnormalities of the digital‐and palmar ridge‐pattern. Contrary to males, in carriers as well as in mentally retarded females without fragile X, fingerprints with low ridge‐counts were found.Common to all mentally retarded patients, but more pronounced in males with fragile X, abnormal palmar creases and hand‐measurements were observed. These findings probably are related to prenatal retarded growth of the length of the palma and of the middle‐finger.
X‐linked Ehlers‐Danlos syndrome type V; the next generation
Authors: Beighton Peter , Curtis Diana 
Published: July 2010

Two English families with the X‐linked form (Type V) of the Ehlers‐Danlos syndrome (EDS) who were investigated almost 20 years ago have been re‐studied. In one family, the potentially heterozygous sister of 3 affected brothers had born two sons, of whom one has EDS. The 3 brothers had all procreated, producing a total of 2 sons and 3 daughters, all of whom are clinically normal. These pedigree data provide further evidence to support the syndromic identity and X‐linked mode of inheritance of this form of the EDS.In the second family, two affected brothers had both procreated; one had produced three normal offspring, while the other had a son with soft extensible skin and a daughter with articular hypermobility. The syndromic status of this kindred is uncertain.Serum copper and ceruloplasmin concentrations in affected males and obligate carrier females in both families were normal. Cytogenetic investigations, including high resolution banding, yielded normal results.
Expression of X‐linked hypohidrotic ectodermal dysplasia in six males and in their mothers
Authors: Söderholm Anna‐Lisa , Kaitila Ilkka 
Published: July 2010

Six male patients with confirmed X‐linked hypohidrotic ectodermal dysplasia and their mothers were studied to determine the variation of expressivity in patients and heterozygotes, major problems of the patients, and to find a clue to pathogenesis.The number of teeth, conic in shape, in patients varied from none to 14. In addition to hypohidrosis and hypotrichosis, dry skin, reduced salivation, hoarseness and hypoplasia of the nipples were common signs. Five patients had frequent respiratory infections.The mothers lacked more than four permanent teeth, one mother had hypodontia in the deciduous dentition.The sweat pore counts were low in patients, and lower than normal in the mothers.All patients carried β‐hemolytic streptococci, four of them group A either in nose or pharynx, without symptoms. Immunoglobulin values, including IgA were normal in serum and saliva.Unexpectedly, serum parathyreoid hormone concentrations both in patients and mothers were low.The major problem of the families was the risk of hyperpyrexia due to hypohidrosis, but the patients' concern was mostly because of their facial appearance.
Heritable fragility at 11q13 and 12q13
Authors: Smeets D. F. C. M. , Scheres J. M. J. C. , Hustinx T. W. J. 
Published: July 2010

The chromosomes of two mentally retarded probands were investigated because they were suspected of having the fragile X syndrome. However two other fragilities were detected. In one patient a fra(11)(q13) was found and in the other a fra(12)(q13). Family studies revealed that both fragile sites were real heritable ones.Besides these two heritable fragile sites, the common fragile site at 3p14 was frequently observed. The effects of BUdR, FUdR and methotrexate on the frequency of the three fragilities were studied.The two heritable fragile sites differed from the common fragile site at 3p14 with respect to their inducibility by FUdR and methotrexate.
Sotos syndrome — autosomal dominant inheritance substantiated
Authors: Winship Ingrid M. 
Published: July 2010

Sotos syndrome, or Cerebral Gigantism is recognised as the syndromic association of mental retardation, macrocephaly and prenatal onset of accelerated growth.A kindred has been investigated in which the father and 4 affected offspring all have the Sotos syndrome. Autosomal dominant inheritance has been postulated in the past, and the family conform to this genetic pattern.