ISSN:0148-7299    

DOI:10.1002/ajmg.1320270302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractCytogenetic investigation on a malformed male infant showed an extra chromosome similar to chromosome 9 in all metaphases studied. GTG, CBG, and G‐11 staining suggested that the extra chromosome was an abnormal 9, permitting the identification of the chromosome constitution as 47,XY, +idic (9) (pter→q13→

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThis study has attempted to assess the burden imposed by congenital anomalies in terms of postnatal mortality and morbidity, which were in turn used to classify anomalies as severe and mild types. Factors studied were postnatal mortality through age 7 years and morbidity, as measured by neurologic and psychologic abnormalities, histories of major surgery, prolonged hospitalization, and chronic infections. The study was based on a prospective study of 52,332 liveborn singletons of the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. In general, the highest degree of burden was observed in syndromes and sequences, followed by multiple and single major anomalies. The burden due to major abnormalities as measured by attributable risk ranged from 0.436 for prolonged hospitalization up to one year, to 0.010 for chronic infections in subjects 1–7 years of age. In terms of mortality, the total attributable risk was 0.164, and the mean potential years of life lost was 5,020 per 10,000 population, which is considerably greater than that reported in other studies. An index constructed from mortality, neurologic, psychologic, and surgical variables provides a reasonable and objective means for classifying anomalies into severe and mild type

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractA study was conducted in a sample of 140 children with sickle cell anemia to evaluate the relationship between hematological variables (%HbF, %HbA2, %Hb, and mean cell volume) and disease severity. A patient's severity status was determined by whether he/she was hospitalized, had a transfusion, and/or had a pain crisis at 2 evaluation periods; the first was based on a patient's history taken at the initial assessment visit to the Wayne State Comprehensive Sickle Cell Center, and the second was based on a 1–3 year follow‐up at the center. Fetal hemoglobin was a strong predictor of a patient's hospitalization and transfusion status. A decrease in %HbF of 4.76% (one SD of %HbF) was associated with a 3.58 fold (95% confidence interval, 1.18–7.28) greater odds of being hospitalized both prior to initial assessment and on follow‐up, compared to not being hospitalized at either evaluation. Similarly, a decrease in %HbF of 4.76% was associated with a 5.56 fold (95% confidence interval, 1.67–18.96) greater odds of having a transfusion both prior to initial assessment and on follow‐up compared to not having a transfusion at either evaluation. Patients who were both hospitalized and transfused at initial assessment and on follow‐up (n = 12) had a mean %HbF of 7.59%, while patients who were not hospitalized or transfused at either evaluation (n = 19) had a mean %HbF of 13.61%. Fetal hemoglobin was not a significant predictor of pain crises in this sample of patients. None of the other hematological variables were significant predictors of disease severity in this study. The strong relationship between %HbF and disease severity identified in this study suggests that a single %HbF measurement may be useful in predicting important aspects of the clinical course of children with sickl

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractTwo sibs are reported with Walker‐Warburg syndrome including hydrocephalus, agyria, anterior chamber dysgenesis, and encephalocele. In addition, both had cleft lip and cleft palate and intrauterine growth retardation, findings not previously noted in this conditio

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe chicken embryo is a useful animal model for investigating problems in developmental biology and teratology. Here we report data that further define the causes of 2 different patterns of malformation (one associated with amnion abnormalities, the other with isolated neural tube defects) and death induced by making a window in the shell and subshell membranes during the first day of incubation. The interpretation of these data suggests to us the following hypotheses. An early amnion deficit spectrum or syndrome (EADS) in chicken embryos is caused by a brief (less than 10 sec) perturbation that occurs during the windowing procedure. This perturbation results in an acute increase in mechanical tension to the developing embryo and support structures, dehydration localized to the area of the blastoderm, and/or increased friction between the blastoderm and overlying vitelline and shell membranes. Isolated neural tube defects (NTDs) are caused by a longer perturbation (>3 hr) consisting of increased mechanical stress across the blastoderm. The mechanical stress is associated with the introduction of a new air space over the animal pole of the yolk during windowing. The new air space causes the shape of the yolk to change (ie, to be deformed), resulting in an increase in mechanical tension across the vitelline membrane and blastoderm. NTDs involving the head are associated with significant early embryonic mortality, whereas those involving the trunk are not. Death may also be caused by cardiovascular anomalies observed in EADS. It is concluded that disturbances in morphogenesis and death in this model are, therefore, the result of extrinsic forces (eg, mechanical stress, localized dehydration, or friction) acting on different tissue types at various critical times in development. Intensity and duration of these forces on the developing blastoderm are important variables.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractWe report on five patients with 45,X/46,XY mosaicism. In these subjects, as well as in 58 individuals from the literature with a similar chromosome constitution, we did not find a preponderance of 46,XY cells among patients showing ambiguous to abnormal male external genitalia when compared to those patients with slight or no virilization. However, the average frequency of 46,XY cells in blood in these mosaic individuals suggests that this sample includes mainly individuals whose mosaicism originated early in embryonic cell division. Those individuals whose mosaicism originated later are not significantly represented in this sample and would have higher frequencies of 46,XY cells. These individuals would be excluded from an intersex sample if they had well‐virilized genitalia. This ascertainment bias suggests that the degree of virilization depends on the frequency of 46,XY cell

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractIn this study we estimate the frequency of carriers of chronic (type I) Gaucher disease among Ashkenazi Jews by examining the glucocerebrosidase activity in leukocytes in a population of 635 blood donors (441 Ashkenazi) and 57 obligatory heterozygotes. Estimation using the defect in the enzyme glucocerebrosidase (beta‐glucosidase) in leukocytes is complicated by the existence of considerable overlap between enzyme activity in normals and in heterozygotes. The assay was carried out with a natural substrate labeled with14C. Discriminant analysis was used to establish an optimal cutoff point between the obligatory heterozygotes and normal (non‐Ashkenazi) subjects for the purpose of estimating frequency of carriers. Applied to the Ashkenazi group, the cutoff point identified 3.17% as heterozygotes. Corrected for errors in classification, the carrier rate was estimated as 4.67%. This figure is in good agreement with a carrier rate of 4% estimated from the number of known cases of clinical Gaucher disease ascertained in Isr

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractRecent advances in molecular biology provide measures of genotypes at loci involved in lipid metabolism. Genotypes for apolipoprotein E (apo E) and quantitative levels of total plasma cholesterol, betalipoprotein, and triglycerides were measured in a sample of 223 unrelated individuals from Nancy, France. The frequencies of the ε2, ε3, and ε4 alleles are 0.13, 0.74, and 0.13, respectively, in this sample. Significant differences among apo E genotypes were detected for these lipoprotein phenotypes. The average effect of the ε2 allele was to reduce total plasma cholesterol and betalipoprotein levels by 0.52 mmol/L and 0.98, respectively, while the ε4 allele raised these levels by 0.26 mmol/L and 0.61, respectively. Apo E genotype specific correlations suggest that this locus also has an effect on the coordinated metabolism between cholesterol and triglycerides. We infer that approximately 17% of the genetic variability in total plasma cholesterol may be attributable to this apo E polymorphism. No other single locus has been identified with such a large contribution to cardiovascular disease risk factors in the general popula

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractWe describe the clinical and genetic details of a series of microcephalic patients who were referred to the Genetic Counselling Service for the West of Scotland. There were 29 isolated cases of microcephaly and 9 families with recurrent microcephaly. The sib recurrence risk was 19%, which reflects the high incidence of autosomal recessive microcephaly in this series. There was evidence for several varieties of recessive microcephaly. The most frequent, affecting 5 sib pairs, was associated with spastic quadriplegia, seizures, and profound mental handicap.In 15 families with one microcephalic child, prenatal diagnosis by serial ultrasound scans was undertaken in 21 subsequent pregnancies. Four recurrences of microcephaly were detected in the third trimester and one recurrence was missed because no scans were performed after 24 wk gestation when the ultrasound measurements indicated satisfactory head growth. The main reason for late diagnosis of affected fetuses was that head growth did not slow appreciably until the last trimester. The high recurrence risk in this prospective series emphasizes the contribution of autosomal recessive inheritance of microcephaly amongst patients of our Genetic Counselling Service.

ISSN:0148-7299    

DOI:10.1002/ajmg.1320270311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY