摘要:

A highly inbred kinship is described, in which 19 individuals were afflicted with bilateral profound microphthalmia without associated anomalies and with normal intelligence. Autosomal recessive inheritance is demonstrated. This kindred is instructive for genetic counseling since the affected individuals always have bilateral microphthalmia in the absence of other affected organ systems.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03458.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Experience with higher resolution banding techniques is described. Cell synchronization and different chemicals which delay the mitotic condensation process were tried. None of these agents alone was able to induce undercondensation in a sufficient way in any of the patients investigated. Of the banding techniques, GTG banding proved preferable, but in some special cases RBA banding will be more informative.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03459.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Seventy patients were selected to cover the range of variability in clinical expression of Niemann‐Pick disease group C (NP‐C). Their individual main clinical features and course of the disease (age at discovery and type of visceromegaly, age at onset and first neurological manifestation, later neurological symptoms) are schematically described. In cultured skin fibroblasts from these patients, sphingomyelinase activities measuredin vitro showed decreased values only in approximately half of the cases, and when the metabolic fate of [14C]‐sphingomyelin was studied in living cell cultures, still 20% of the cases had a normal hydrolysis rate. Esterification of exogenous cholesterol was investigated in cell lines from these and 5 additional patients and in 21 of their parents. Using a non‐lipoprotein [3H]cholesterol source, very low esterification rates were obtained in more than 90% of the cases. All the numerous other pathological conditions studied, including Niemann‐Pick disease types A and B, gave normal results. A more sensitive method was elaborated, in which the cells were challenged with pure human low density lipoproteins (LDL) and the early rate of esterification studied. With the latter procedure, a pronounced deficiency could also be demonstrated in the few cases which had shown a milder impairment using a [3H]cholesterol source, and intermediate rates of esterification were obtained in heterozygotes. Discrimination of these difficult cases and of heterozygotes could also be achieved replacing LDL with total unfrozen human serum. Correlations were established between given clinical phenotypes and the severity of the biochemical lesion. Defective intracellular cholesterol esterification is further established as an intrinsic feature of NP‐C, and demonstration of this metabolic alteration appears as a major advance in diagnosing th

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03460.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

The genetic counseling needs of 32 women of normal intelligence at‐risk for having children with the fragile‐X syndrome (FXS) were determined by a questionnaire study which included assessment of their attitudes toward prenatal diagnosis and the option of pregnancy termination. Eighteen (56%) of the women had one or more children with the FXS and 14 (44%) had no affected children. Twenty‐six (81%) of the subjects stated that they would choose to have prenatal diagnosis and 9 (28%) indicated they would terminate an affected pregnancy. There was no significant difference between women who had affected children and those who did not have affected children, nor between Catholics and non‐Catholics regarding acceptance of prenatal diagnosis. Catholic women were less likely to consider pregnancy termination than non‐Catholics, but the majority of subjects (56%) were unsure what they would do if a fetus they were carrying was found to be affected. Issues the subjects considered most important for discussion with a genetic counselor included: 1) availability of treatment, 2) risk for having an affectedgrand child, 3) expectations for future functioning of affected children, and 4) availability of prenatal

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03461.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Partial trisomy 6p with duplications ranging from 6p21 to 6p25–pter is emerging as an established syndrome. We report a case of duplication of 6p (6p23–pter) and deletion of 2q37–qter. Features characteristic of 6p partial trisomy present in the patient are low birth‐weight, and mental and developmental retardation. Major facial features include prominent forehead, flat occiput, multiple ocular abnormalities, low‐set ears, prominent nasal bridge, long philtrum and small pointed mouth. Repeated examinations of the patient from birth to the age of over 5 years revealed that he has infantile autism. Since autistic children are generally not associated with chromosome anomalies, in view of the present case, it is suggested that karyotypic analysis be considered for such children. Where possible, extended study for autism in 6p trisomic children may also be

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03462.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

Endothelial cells are of particular interest for therapeutic strategies in Fabry's disease, because the accumulation of glycosphingolipids in the vascular endothelium as a result of α‐galactosidase A (α‐galA) deficiency is responsible for the major clinical manifestations of the disease. Electron microscopical observations of cultured endothelial cells obtained from the umbilical vein of a hemizygous Fabry fetus showed that the glycosphingolipids are deposited as lamellar material in the lysosomes, as has been found previously for cultured fibroblasts and many different tissues. Mannose 6‐phosphate (man 6‐P)‐receptor mediated and Concanavalin A (ConA)‐mediated uptake of purified α‐galA was attempted in the endothelial cells as well as in cultured fibroblasts from the same fetus. Our results on high‐uptake α‐galA indicate that the endothelial cells do not internalize α‐galA via the man 6‐P receptor. Immunofluorescence studies after addition of the receptor antibody to the cells support the theory that they have no or very few man 6‐P receptors on the surface. Morphological studies did not show lysosomal changes which could suggest that the enzyme is taken up into the endothelial cells; however, we found reproducible modifications of the lysosomes in Fabry fibroblasts after incubation with high‐uptake α‐galA. Cell‐associated α‐galA activity was found in both cell types, when the enzyme was added to cells preincubated with ConA; but the lectin treatment by itself induced considerable ultrastructural changes in the cytoplasm, which ob

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03463.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

A 1‐year‐old girl with an interstitial deletion of the long arm of chromosome 16 is reported. She was characterized by a distinct craniofacial dysmorphism, meningoencephalocele, mild hydrocephalus, short neck, broad great toes and abnormally positioned toes. High resolution GTG and RBG banding analyses revealed a karyotype: 46,XX,del(16) (q13q22)de novo. An analysis of the smallest region of overlap revealed that the critical band region for 16q deletion syndrome is 16

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03464.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

A male patient is reported with a mutation of acid α‐glucosidase causing an altered Km toward natural substrates. Cardiac arrhythmia was found at 12 years of age, and he died of heart failure at 15 years. No skeletal muscle involvement was observed either clinically or histologically. Acid α‐glucosidase activity in fibroblasts was moderately low (43% of the control mean) with normal Km for 4‐methylumbelliferyl α‐D‐glucoside. The hydrolysis of glycogen was markedly decreased (14% of the control mean), and the Km for maltose was increased 4‐fold and for glycogen 5‐fold. The biosynthesis and the posttranslational processing of the mutant enzyme appeared normal, but the total amount of the enzyme was lower than normal. This mutant enzyme comigrated with normal acid α‐glucosidase on starch gel electrophoresis, and not with the rare isozyme, acid α‐glucosidase 2. A possible role of this mutant enzyme in the pathogenesis of this disease and the relationship to glycoge

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03465.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

In this report we present a malformed female newborn with partial trisomy 20q who was the unbalanced product of a paternal 8p/20q translocation (46,XY,t(8;20) (p23.1;q11)).

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03466.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

A normocephalic, severely retarded boy with a family history suggesting aqueductal stenosis was found by computerized tomography to have aqueductal stenosis. His parents' concurrent pregnancy was monitored by ultrasonography and amniocentesis; these disclosed a male fetus which developed marked hydrocephalus after the 20th week. The pregnancy was terminated and an autopsy of the fetus demonstrated several major CNS malformations in addition to a very narrowed aqueduct. This case illustrates the diffuse CNS disease present in at least some cases of X‐linked aqueductal stenosis (XLAS) and the importance of considering this variable syndrome in normocephalic, non‐dysmorphic mentally retarded males. Important aspects of the prenatal diagnosis of XLAS are also illustra

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1988.tb03467.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY