Patients With an Unclassified Genetic Variant in the BRCA1 or BRCA2 Genes Show Different Clinical Features From Those With a Mutation

2005 ◽  
Vol 23 (10) ◽  
pp. 2185-2190 ◽  
Author(s):  
Encarna B. Gómez-García ◽  
Ton Ambergen ◽  
Marinus J. Blok ◽  
Arthur van den Wijngaard
Keyword(s):  
Standard Deviation ◽  
Family History ◽  
Clinical Features ◽  
Predictive Models ◽  
Genetic Variant ◽  
Pathogenic Mutation ◽  
Unclassified Variant ◽  
The Family ◽  
Novel Variants ◽  
Combined Data

Purpose To obtain and compare the probabilities of finding a mutation in the BRCA1 or BRCA2 genes, the clinical features, and the family history among patients with an unclassified variant (UV) and those with a pathogenic mutation. Patients and Methods The study included 70 patients: 24 with a UV (BRCA1, n = 4; BRCA2, n = 19; both, n = 1), and 46 with a mutation (BRCA1, n = 32; BRCA2, n = 14). Two of the UVs were novel variants; the rest had been reported previously as UVs. Probabilities of finding a mutation were retrospectively obtained using BRCAPRO and Myriad II programs. Results The probability to detect a mutation was significantly lower in the group of patients with a UV than in those with a mutation (BRCAPRO [mean ± standard deviation], 0.297 ± 0.312 v 0.627 ± 0.315, P = .001; and Myriad II, 0.124 ± 0.090 v 0.283 ± 0.176, P = .001, respectively). Independent predictive factors of finding either a UV or a mutation were number of affected relatives (2.9 ± 1.4 v 4.0 ± 1.9; P = .039) and number of tumors among relatives (3.3 ± 1.4 v 4.4 ± 1.8; P = .031), respectively. Conclusion The combined data about the predictive models show significant differences between both groups. Individual probabilities can be regarded as a help to guide the clinical management of patients with a UV in those genes. However, a definitive conclusion about the pathogenicity of a UV can not be obtained from the clinical features alone, but only in combination with biochemical and epidemiologic data.

DOMINANT INHERITANCE OF DIABETES INSIPIDUS

PEDIATRICS ◽  
1953 ◽  
Vol 11 (3) ◽  
pp. 246-254
Author(s):  
C. B. PENDER ◽  
F. CLARKE FRASER
Keyword(s):  
Family History ◽  
Diabetes Insipidus ◽  
Clinical Features ◽  
Intravenous Injection ◽  
Marked Reduction ◽  
Diagnostic Value ◽  
Urinary Flow ◽  
Dominant Inheritance ◽  
The Family ◽  
Inheritance Of Diabetes

The clinical features of diabetes insipidus are described in a family showing dominant inheritance of this condition. Forty affected individuals in six generations are listed. Two members of the family, investigated in hospital, showed no alteration of urinary flow in response to the intravenous injection of saline, but a marked reduction in flow following the injection of pitressin, thus confirming the diagnosis of diabetes insipidus due to pitressin deficiency. An exceedingly great urinary output is not necessarily a feature of the disease. The diagnostic value of the family history is emphasized.

Antithrombin III Alger: A New Homozygous AT III Variant

1986 ◽  
Vol 55 (02) ◽  
pp. 218-221 ◽  
Author(s):  
A M Fischer ◽  
P Cornu ◽  
C Sternberg ◽  
F Mériane ◽  
M D Dautzenberg ◽  
...  
Keyword(s):  
Family History ◽  
Antithrombin Iii ◽  
Antigen Concentration ◽  
Crossed Immunoelectrophoresis ◽  
The Family ◽  
At Iii ◽  
Molecular Abnormality ◽  
Slow Moving ◽  
Cofactor Activity ◽  
Plasma Heparin

SummaryA qualitative abnormality of antithrombin III (AT III) was found in the plasma of a 41-year old patient. The plasmatic AT III antigen concentration was 130% and the progressive anti-F IIa and anti-F Xa activities were normal (105% and 137%). The plasma heparin cofactor activity was less than 10%, when measured by F Ila or F Xa inhibition. Crossed immunoelectrophoresis of AT III in the presence of heparin revealed in the plasma an abnormal slow-moving peak. When tested by affinity chromatography on heparin Sepharose, this abnormal AT III did not bind to heparin. Among the investigated relatives, 5 subjects had normal AT III levels, whatever the test used, the nine others having reduced levels of antithrombin heparin cofactor activity (45-61%) but normal levels of immunoreactive AT III (97-122%). Consanguinity was found in the family history. We therefore considered our patient as homozygous for an AT III molecular abnormality affecting the binding site for heparin.

The Dupont family: collectors, dealers and naturalists in nineteenth-century Paris

2016 ◽  
Vol 43 (2) ◽  
pp. 191-207 ◽  
Author(s):  
Richard Mearns ◽  
Laurent Chevrier ◽  
Christophe Gouraud
Keyword(s):  
Nineteenth Century ◽  
Family History ◽  
Natural History ◽  
North Africa ◽  
Special Interest ◽  
Early Life ◽  
Anatomical Models ◽  
The Family ◽  
Small Collection

In the early part of the nineteenth century the Dupont brothers ran separate natural history businesses in Paris. Relatively little is known about their early life but an investigation into the family history at Bayeux corrects Léonard Dupont's year of birth from 1795 to 1796. In 1818 Léonard joined Joseph Ritchie's expedition to North Africa to assist in collecting and preparing the discoveries but he did not get beyond Tripoli. After 15 months he came back to Paris with a small collection from Libya and Provence, and returned to Provence in 1821. While operating as a dealer-naturalist in Paris he published Traité de taxidermie (1823, 1827), developed a special interest in foreign birds and became well known for his anatomical models in coloured wax. Henry Dupont sold a range of natural history material and with his particular passion for beetles formed one of the finest collections in Europe; his best known publication is Monographie des Trachydérides (1836–1840). Because the brothers had overlapping interests and were rarely referred to by their forenames there has been confusion between them and the various eponyms that commemorate them. Although probably true, it would be an over-simplification to state that birds of this era named for Dupont refer to Léonard Dupont, insects to Henry Dupont, and molluscs to their mother.

scholarly journals Are Family Firms More Levered? An Analysis of Family and Non-Family Firms

SAGE Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 215824402110223
Author(s):  
Jahanzaib Haider ◽  
Abdul Qayyum ◽  
Zalina Zainudin
Keyword(s):  
Family Firms ◽  
East Asian ◽  
Ordinary Least Squares ◽  
Maturity Structure ◽  
The Family ◽  
Asian Economies ◽  
The Board Of Directors ◽  
East Asian Economies ◽  
Combined Data

This study analyzes the leverage policies of the family and non-family firms of eight East Asian Economies (Hong Kong, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, and Taiwan) by using combined data of 690 family and non-family firms with 3,224 firm–years over the period 2006–2010. This study has used an ordinary least squares (OLS) regression for analyzing the data for the first question, while for the second question, logit regression has been used as the dependent variable (a binary variable). Prior research on family and non-family firms has revealed that family firms issue less (high) debt than non-family firms. Our analysis on a sample of East Asian Economies discloses that family firms have significantly different leverage levels than non-family firms, but their signs are not consistent. On the contrary, when the owner works as CEO/Chairman or member of the Board of Directors, then the family firms issue less debt than the non-family firms. Besides that, this study adds a new question that has not been addressed in the prior studies. The new question has focused on the speed of leverage adjustment. It is found that family firms and non-family firms regarding their debt maturity structure (short-term debt and long-term debt), the speed of leverage adjustments, and their decision to issue securities (i.e., debt vs. equity) are not significantly different. This study concluded that though family firms have a strong influence on each economy, but in South-East Asian countries, leverage policies of the family firms are not much different than that of non-family firms.

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

Relationship of birth season to clinical features, family history, and obstetric complications in schizophrenia

1996 ◽  
Vol 64 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Daniel Dassa ◽  
Pak C. Sham ◽  
Jim van Os ◽  
Kathryn Abel ◽  
Peter Jones ◽  
...  
Keyword(s):  
Family History ◽  
Clinical Features ◽  
Obstetric Complications ◽  
Birth Season ◽  
Relationship Of

FAMILY TENSION AS A CAUSE OF COLIC IN INFANTS

PEDIATRICS ◽  
1956 ◽  
Vol 18 (5) ◽  
pp. 835-836
Author(s):  
John C. Cobb
Keyword(s):  
Family History ◽  
Allergic Disease ◽  
Family Members ◽  
Clinical Impression ◽  
Family Histories ◽  
The Family

A study of colic in infancy was undertaken as part of the Yale Rooming-In Project. The longitudinal records of 98 infants who were study subjects were analyzed with respect to incidence, duration, and severity of colic. Forty-eight of the infants were classified as fussy or colicky and 50 as contented. Because I had formed the clinical impression that allergy was an important contributing factor in the causation of colic, careful family histories were taken for all of these infants with particular attention to allergic disease in any member of either parent's family. An adequate family history was obtained in 95 of these infants. These data were analyzed both according to the incidence of allergic disease and according to the severity of allergic disease in family members. Among the relatives of the 45 "fussy" or "colicky" infants 7.3 per cent had severe allergy, 17.7 pen cent had mild allergy and 74 per cent had little or no allergy. Among the relatives of the 50 contented infants 7.6 per cent had severe allergy, 14.7 per cent had mild allergy and 77 per cent had no allergy. The family histories included a total of 957 relatives. The 45 families of the babies who were fussy or colicky were divided as follows as to amount of allergy among the relatives. In 7 families there was much allergy, in 30 families there was some allergy and in 8 families there was little or no allergy. The [See Table I in Source PDF] families of the 50 contented infants were divided as follows, in 7 families there was much allergy, in 33 there was some allergy and in 10 there was little on no allergy.

Association between gastric cancer and the family history of gastric cancer

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Hyo Geun Choi ◽  
Wook Chun ◽  
Kuk Hyun Jung
Keyword(s):  
Gastric Cancer ◽  
Family History ◽  
The Family ◽  
History Of
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