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PubMed1990

Identification and metabolic characteristics of an apolipoprotein C-II variant isolated from a hypertriglyceridemic subject.

The very low density lipoprotein (VLDL) apolipoproteins from a Type IV hypertriglyceridemic Caucasian subject (plasma TG: 645 mg/dl) and his brother (plasma TG: 328 mg/dl) were separated by isoelectric focusing gel electrophoresis (IEF) and found to contain two isoforms of apoC-II, identified by immunoblot. These corresponded to normal apoC-II-1 (isoelectric point: pI 4.88) and a variant isoform (apoC-II-v, pI 4.74). The pI of C-II-v was not altered by neuraminidase treatment, indicating that it was not sialylated. The concentration of total immunoreactive C-II in VLDL was elevated (18 mg/dl vs normal; 5.0 +/- 2 mg/dl) but similar to that in other Type IV subjects. In VLDL, which contained 90% of the plasma immunoreactive apoC-II, the ratio (by IEF) of C-II-1:C-II-v was 2:1, whereas in high density lipoproteins (HDL) the ratio was 1:1. VLDL apoB turnover was measured after the pulse injection of 125I-labeled VLDL. VLDL apoB kinetic parameters for the proband and four Type IV subjects were similar: production rate, 28 mg/kg per day versus 30 mg/kg per day; fractional catabolic rate, 1.62.day-1 versus 1.96.day-1; and pool size, 17 mg/kg versus 18 mg/kg. The decline in VLDL triglyceride (TG) after the infusion of heparin (9,000 IU over 4 h) was also similar to that observed in Type IV subjects. In VLDL, the fractional catabolic rates of apoC-II-1 and C-II-v were similar (C-II-1: 0.31.day-1, C-II-v: 0.29.day-1) whereas in HDL, although similar to each other, the rates were greater than in VLDL (C-II-1: 0.48.day-1, C-II-v: 0.44.day-1). VLDL and HDL from the proband were normal in their ability to activate bovine skim milk lipase, compared to Type IV VLDL and HDL without C-II-v. Purified apoC-II-1 and apoC-II-v activated the milk lipase to a similar extent (at 1 microgram of C-II; C-II-1: 34 units/h, C-II-v: 35 units/h). Thus, apoC-II-v is a newly recognized isoform of apoC-II-1. It remains to be determined whether this mutation plays a role in the genesis of hypertriglyceridemia.

Adult↗

PubMed1988

Clonal analysis of untreated non-Hodgkin's lymphoma utilizing immunoglobulin gene rearrangement and immunophenotype.

We have prospectively examined 66 consecutive initial diagnostic lymph node biopsies from unselected patients suspected of having malignant lymphoma for clonal immunophenotypic and immunogenotypic markers. By morphological and cell surface phenotypic criteria 52 had non-Hodgkin's lymphoma derived from the B-cell lineage and in these we compared surface immunoglobulin criteria for clonality with immunoglobulin gene rearrangement as detected by JH, C kappa, and C lambda gene probes. We found that the addition of BglII and HindIII double digests to the standard BamHI and EcoRI restriction enzymes made it possible to detect rearrangement in the vast majority of lymphomas and that rearrangement of both JH alleles is the rule. A rearranged heavy and/or light chain gene was detected in 47 of 52 (91%) tumors and the JH probe alone detected rearrangements in 87% of tumors when multiple restriction enzymes were used. In contrast, surface immunoglobulin, the standard clonal marker for monoclonal B-cell malignancy, was either undetectable or did not exhibit light chain restriction in 29 of 52 tumors as detected by flow cytometric analysis. Further, in 24 of these 29 tumor DNAs we could detect an Ig gene rearrangement. In follicular (nodular) lymphoma which often gives ambiguous immunophenotypic results by cell suspension techniques, monoclonal gene rearrangements were detected in 16 of 18 tumor DNAs. Monoclonal surface immunoglobulin was detected in only 8 of 18 of this subset of cases. The 52 tumors were also analyzed for potential oligoclonality. We found that the use of BglII, a restriction enzyme that closely spanned the JH region, increased the sensitivity of detecting rearrangements and facilitated the identification of isotype switch variants. In only a single (1 of 52) tumor DNA were more than two rearranged bands seen with JH, C kappa, and C lambda probes, suggesting a multiclonal origin. Additional cases thought to potentially represent oligoclonality by immunophenotypic criteria proved to be isotype switch variants. We conclude that Ig gene rearrangement is an extremely sensitive method for defining monoclonality in lymphoma cell populations, particularly if multiple restriction enzymes are used, and that the vast majority of the clonal diversity seen in initial diagnostic biopsies is the result of isotypic switch within a given clone rather than true oligoclonality.

B-Lymphocytes↗

PubMed1986

Identification of homozygosity for a human apolipoprotein A-I variant.

An apolipoprotein (apo) A-I variant, previously described in two Norwegian families (Schamaun et al. 1983. Hum. Genet. 64: 380-383), represents a mutation in apoA-I in which a single amino acid substitution of lysine for glutamic acid has taken place at residue 136. An offspring resulting from intermarriage between the two families is genotypically homozygous for this variant. He is the first individual discovered to be homozygous for any of the apoA-I variants. Analysis of lipid data collected from these families indicates one or more lipid abnormalities. The low density lipoproteins (LDL) of subjects having this apoA-I variant demonstrate a compositional abnormality. The plasma cholesterol concentration in the homozygous subject is low because of the extremely reduced levels of LDL and apoB, a property shared by some of his first-degree relatives. However, because of the presence of apoE2 in this family, it is not possible to definitively link these lipid abnormalities to the presence of the A-I variant.

Adolescent↗

PubMed1985

[Acoasmatic hallucinosis in tardive schizophrenia].

A study of late schizophrenia manifested in the syndrome of involutional paranoid has allowed the identification of the clinical variant of such psychoses (44 observations) differing from the classical forms in that the clinical picture was predominated by elementary acoustic hallucinations (acoasms). The phenomenological analysis has established that the formation of the clinical picture is determined by acoasms and also the resulting delirium of imagination and delirious interpretations. Two major variants of such psychoses have been specified and described ("the syndrome of acoasmatic hallucinosis" and "the hallucinational-delirious syndrome with the predominance of acoasms"). It has been established that each of these syndromal variants may determine the picture of the disease throughout its course or be one of the sequential stages of its development.

Aged↗

PubMed1984

Plasma lipoproteins: apolipoprotein structure and function.

Plasma lipoprotein metabolism is regulated and controlled by the specific apolipoprotein (apo-) constituents of the various lipoprotein classes. The major apolipoproteins include apoE, apoB, apoA-I, apoA-II, apoA-IV, apoC-I, apoC-II, and apoC-III. Specific apolipoproteins function in the regulation of lipoprotein metabolism through their involvement in the transport and redistribution of lipids among various cells and tissues, through their role as cofactors for enzymes of lipid metabolism, or through their maintenance of the structure of the lipoprotein particles. The primary structures of most of the apolipoproteins are now known, and various functional domains of these proteins are being mapped using selective chemical modification, synthetic peptides, and monoclonal antibodies. Furthermore, the establishment of structure-function relationships has been greatly advanced by the identification of genetically determined variants of specific apolipoproteins that are associated with a disorder of lipoprotein metabolism. Future studies will rely heavily on the use of recombinant DNA technology and site-specific mutagenesis to elucidate further the correlations between structure and function and the role of specific apolipoproteins in lipoprotein metabolism.

Apolipoprotein A-I↗

PubMed1994

A non-classical translocation involving 17q12 (retinoic acid receptor alpha) in acute promyelocytic leukemia (APML) with atypical features.

Acute promyelocytic leukemia (APML) almost always involves a chromosomal translocation t(15:17) that results in the fusion of the retinoic acid receptor alpha (RAR alpha) gene with a transcription factor gene called PML. Several cases of APML with t(11;17) have recently been described, involving fusion of the RAR alpha gene with a new zinc finger gene named PLZF. We report here a second non-classical translocation, t(5;17), with a rearranged RAR alpha gene in a child with APML. Based on restriction endonuclease analysis, the rearrangement of RAR alpha occurred within the second intron, the common breakpoint site for t(15;17). The leukemic cells in the bone marrow aspirate were a mixture of hypergranular and hypogranular bilobed promyelocytes. Although less than 1% abnormal promyelocytes were identified after induction therapy, cytogenetics revealed persistent t(5;17). Therefore, the child was treated with all-trans-retinoic acid (ATRA). There was no disease progression, and one marrow was interpreted as remission, with confirmation by cytogenetics which failed to reveal the translocation. However, disease reoccurred shortly after completion of ATRA. This poor response to ATRA may be an additional characteristic associated with non-classical translocations in APML. The identification of a second variant translocation involving the RAR alpha gene in APML suggests yet another RAR alpha rearrangement related to neoplastic myelopoiesis.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Unusual oesophageal cancer: a report of four cases.

The prognosis for carcinoma of the oesophagus is generally dismal especially when patients present late. Any clues to early diagnosis and management and identification of rapidly progressive variants are therefore helpful. Reports and review of the literature are presented with respect to four unusual cases of oesophageal carcinoma treated in the University of Ilorin Teaching Hospital in 1985 and 1986. Four men aged 59, 60, 55 and 60 years respectively presented with multiple polypoid carcinoma of the oesophagus, malignant oesophago-bronchial fistula at the level of the left main stem bronchus, achalasia co-existing with oesophago-gastric carcinoma and a small focus of carcinoma of the distal thoracic oesophagus presenting with widespread thoracic metastases and malignant pleural effusion mimicking advanced bronchogenic carcinoma. The unusual clinico-pathological features with the autopsy findings in the last case can influence diagnosis, management and prognosis of oesophageal cancer in general and of such cancer associated with pre-malignant conditions like achalasia and oesophageal polyps in particular.

Adenocarcinoma↗

PubMed1998

A foodborne outbreak of Salmonella enteritidis vehicled by duck and hen eggs in southern Italy.

A foodborne outbreak of Salmonella enteritidis PT4 is described. This microrganism was detected in a home-made dessert, in the duck and hen eggs used for its preparation and in faecal samples of six persons involved in the outbreak. PCR ribotyping revealed that all the strains shared a profile of S. enteritidis never previously identified in southern Italy and quite different from that of the strains simultaneously isolated in the same geographic area. The possible identification of a clonal variant of S. enteritidis PT4 host-adapted to duck is hypothesized.

Animals↗

PubMed2006

Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. PATIENTS AND METHODS: A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. RESULTS: During these mutational screening procedures one case presented three mutations classified in the Breast Cancer Information Core Database as unknown variants. These were 655A/G found in exon 8 of BRCA1, 1575T/C and 1767A/C found in exon 11 of the same gene. The identification of the three unknown variants in the proband (16SIRIO) and in her mother and sister indicates that such alterations exist in cis. CONCLUSIONS: Our results suggest that the charge and stechiometry variations determined by the changes in the amino acids Y179C, F486L and N550H might produce an effect on the conformation of the protein and, consequently, on its function.

Adult↗

PubMed2026

Molecular residual disease assessment in colorectal and bladder cancer by somatic structural variant analysis of cell-free DNA whole-genome sequencing data.

BACKGROUND: Whole-genome sequencing (WGS)-based methods for circulating tumor DNA (ctDNA) detection typically rely on tumor-informed identification of somatic single nucleotide variants (SNVs). Somatic structural variants (SVs) are another type of cancer-specific genomic alteration, which owing to their larger genomic footprint and unique breakpoint junctions, are easier to distinguish from sequencing noise than SNVs. They are, however, rarely used for ctDNA detection because of (1) artifacts from WGS procedures that SV callers may falsely interpret as genuine SVs. This makes it difficult to establish high-confidence SV catalogos from short-read tumor WGS and can cause false-positive ctDNA detections. (2) Lack of robust strategies to quantify SV-supporting reads in plasma WGS. To address these barriers and enable integration of SV biomarkers into WGS-based ctDNA detection, we present a bioinformatic framework for algorithmic curation of somatic SV calls from fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tumors, coupled with a novel approach for sensitive, accurate mapping and quantification of SV breakpoint-supporting reads in plasma WGS. METHODS: Tumor, normal and plasma WGS data from 144 patients with stage III colorectal cancer was used to establish the bioinformatic framework. This included ~30x WGS data from 1564 serially collected plasma samples. The framework was validated using tumor/normal/plasma WGS data from 32 patients with muscle-invasive bladder cancer. SV-based ctDNA detection was benchmarked against previously published SNV-based ctDNA results for the same samples. RESULTS: After curation of SV calls and quantification in plasma WGS, our SV-based approach enabled robust ctDNA detection with overall specificity exceeding 99% in plasma samples. Furthermore, we observed strong concordance (Pearson’s r > 0.93, p < 2.2 × 10− 16) between ctDNA-positive samples identified by our SV-based method and previous SNV-based analyses, validating the reliability of our approach. Finally, we demonstrated application of the method in an independent bladder cancer cohort, highlighting its generalizability and potential clinical use. CONCLUSIONS: We provide a bioinformatic framework that establishes somatic SVs as ultra-specific biomarkers for WGS-based, tumor-informed ctDNA detection. The approach delivers specific detection even when the SV catalogos are established from FFPE samples. The SV framework can stand alone or enhance SNV-based analysis pipelines.

Humans↗

PubMed2002

Expression of a novel HsMCAK mRNA splice variant, tsMCAK gene, in human testis.

Identification of specifically expressed genes in the adult or fetal testis is very important for the study of genes related to the development and function of the testis. In this study, a human adult testis cDNA microarray was constructed and hybridized with 33P-labeled human adult and embryo testis cDNA probes, respectively. After differential display analyzing, a number of new genes related to the development of testis and spermatogenesis had been identified. One of these new genes is tsMCAK. tsMCAK was expressed 2.62 folds more in human adult testis than fetal testis. The full length of tsMCAK is 2401 bp and contains a 2013 bp open reading frame, encoding a 671-amino-acid protein. Sequence analysis showed that it has a central kinesin motor domain and is homologous to HsMCAK gene of the somatic cells. Blasting human genome database localized tsMCAK to human chromosome 1P34 and further investigation showed that it is a splice variant of HsMCAK. The tissue distribution of tsMCAK was determined by RT-PCR and it is expressed highly and specifically in the testis. Southern blot studies of its expression in patients with infertility indicated its specific expression in spermatogenic cells and its correlation with male infertility. The above results suggested that tsMCAK is a candidate gene for the testis-specific KRPs and its specific expression in the testis was correlated with spermatogenesis and may be correlated with male infertility.

Adult↗

PubMed2005

Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects.

BACKGROUND: Mutations in ANK2-encoded ankyrin-B underlie long QT syndrome type 4 (LQT4) and various other dysrhythmia phenotypes. OBJECTIVES: The purpose of this study was to determine the prevalence and spectrum of ankyrin-B mutations in a large cohort of unrelated patients referred for LQTS genetic testing and among healthy control subjects. METHODS: Between August 1997 and July 2004, 541 consecutive, unrelated patients (358 females, average age at diagnosis 24 years, average QTc 482 ms) were referred to Mayo Clinic's Sudden Death Genomics Laboratory for comprehensive mutational analysis of the five cardiac channel genes implicated in LQTS: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6). Based on this prior analysis, 269 of 541 cases lacked an identifiable mutation (genotype negative). In this study, targeted mutational analysis of 10 ANK2 exons (36,37,39-46) encoding the critical C-terminal regulatory domain or implicated previously as hosting pathogenic mutations was performed on genomic DNA from 541 patients and 200 control subjects using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing. RESULTS: Overall, 14 distinct nonsynonymous variants (10 novel) were observed in 9 (3.3%) of 269 genotype-negative LQTS patients, 5 (1.8%) of 272 genotype-positive LQTS cases, 4 (4%) of 100 white controls, and 9 (9%) of 100 black controls. Four variants found in controls (L1622I, T1626N, R1788W, and E1813K) were implicated previously as LQT4-associated mutations and displayed functional perturbations in vitro. All genotype-negative LQTS cases hosting ANK2 variants had been diagnosed as "atypical" or "borderline" cases, most presenting with normal QTc, nonexertional syncope, U waves, and/or sinus bradycardia. CONCLUSION: Nonsynonymous ankyrin-B variants were detected in nearly 3% of unrelated LQTS patients and nearly 7% of healthy control subjects. Genotype-negative LQTS patients with a single ANK2 variant displayed nonexertional syncope, U waves, sinus bradycardia, and extracardiac findings. Whether the identification of previously reported functionally significant variants residing in 2% of apparently healthy subjects suggests proarrhythmic potential or potential misclassification warrants further scrutiny.

Adolescent↗

PubMed2006

First detection of canine parvovirus type 2c in pups with haemorrhagic enteritis in Spain.

Canine parvovirus type 2 (CPV-2), the aetiological agent of haemorrhagic enteritis in dogs, includes three antigenic variants, types 2a, 2b and 2c. CPV-2c has been detected initially in Italy and subsequently in Vietnam. We report the first identification of this novel antigenic variant in Spain, where it caused an outbreak of fatal enteritis in basset hound pups in association with canine coronavirus type I and type II. We suggest that this new antigenic variant of CPV-2 could spread throughout Europe and that there is a subsequent need to update current CPV vaccines.

Animals↗

PubMed1987

Calcium antagonists for Prinzmetal's variant angina, unstable angina and silent myocardial ischemia: therapeutic tool and probe for identification of pathophysiologic mechanisms.

The calcium antagonists provide a unique tool to reduce myocardial oxygen demand and prevent increases in coronary vasomotor tone. For patients with Prinzmetal's variant angina, diltiazem, nifedipine and verapamil are extremely effective in preventing episodes of coronary vasospasm and symptoms of ischemia. Unstable angina pectoris is a more complex pathophysiologic syndrome with episodes of ischemia due to increases in coronary vasomotor tone, intermittent platelet aggregation or alterations in the underlying atherosclerotic plaque. Each of the calcium antagonists is effective as monotherapy in decreasing the frequency of angina at rest. Nifedipine is the only calcium antagonist that has been studied in a combination regimen with beta blockers and nitrates for patients with unstable angina, and control of angina is better with the combination regimen than with either form of therapy alone. Although symptoms of myocardial ischemia in unstable angina are reduced by calcium antagonists, these agents do not seem to decrease the incidence of adverse outcomes. Antiplatelet therapy appears to improve morbidity and mortality in patients with unstable angina, suggesting that thrombus formation may play a central role in that disorder. Episodes of silent or asymptomatic myocardial ischemia, identified by ST-segment monitoring, occur in a variety of disorders of coronary disease. Among patients with Prinzmetal's variant angina and unstable angina, episodes of silent ischemia appear to be as frequent as episodes of angina and the calcium antagonists are effective in decreasing episodes of ischemia regardless of the presence or absence of symptoms. Persisting episodes of silent ischemia among patients with unstable angina despite maximal medical therapy identify patients at high risk for an early unfavorable outcome. Among patients with stable exertional angina, episodes of silent ischemia may be up to 5 times as frequent as episodes of angina, and may be due to increases in coronary vasomotor tone, transient platelet aggregation or increases in myocardial oxygen demand. Preliminary experience suggests that calcium antagonists and beta blockers are effective in decreasing episodes of silent ischemia in patients with stable exertional angina and that a combination regimen may be more effective than either form of therapy alone.

Angina Pectoris↗

PubMed2006

Pathogen escape from host immunity by a genome program for antigenic variation.

The vector-borne bacterium Borrelia hermsii, a relapsing fever agent, switches gene expression of a surface protein between different antigenic variants, thereby causing sequential waves of immune escape within hosts and increasing the likelihood of transmission. Analogous programmed systems of antigenic variation occur in African trypanosomes and Plasmodium falciparum. In these examples, switch rates to individual variants differ over a wide range. We studied how B. hermsii determines switch rates in two experimental infections: one where variants were identified by specific antisera and one based on identification by DNA sequence. Unexpressed loci of variant antigens copy into a single expression site at rates determined by extragenic features of silent loci rather than similarity between coding sequences of variants at silent sites and the single expression site. Two elements, in particular, determine switch rates. One set of elements overlaps the 5' ends of the expressed gene and the silent loci; greater sequence identity between elements was associated with a higher switch rate. The second set of elements flanks the expression site on the 3' side and occurs at variable distances downstream from silent loci; the nearer an element to a silent locus, the greater the switch rate of that locus into the expression site. In combination, these two features of the genome provide a simple mechanism to modulate switch rate whereby silent loci form a hierarchy of switch rates into the expression site. Although the switching hierarchy causes changes in individual cells that are stochastic, ordering of variants within hosts is semipredictable.

Animals↗

PubMed1996

The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner.

We report here the identification of cDNAs for three new mouse PDE1C splice variants and the characterization of their kinetics, regulation by Ca2+, sensitivities to inhibitors, and tissue/cellular expression patterns. Sequence analysis indicated that these three cDNAs (PDE1C1, PDE1C4, and PDE1C5), together with our previously reported PDE1C2 and PDE1C3, are alternative splice products of the PDE1C gene. The results from RNase protection analysis and in situ hybridization indicated that the expression of the different PDE1C splice variants is differentially regulated in a tissue/cell-specific manner. Particularly, high levels of PDE1C mRNAs were found in the olfactory epithelium, testis, and several regions of mouse brain such as cerebellar granule cells. All of these splice variants have similar kinetic properties, showing high affinities and approximately the same relative Vmax values for both cAMP and cGMP. However, they responded to Ca2+ stimulation differently. In addition, they show different sensitivities to the calmodulin-dependent phosphodiesterase inhibitors, KS505a and SCH51866. Substrate competition experiments suggested the presence of only one catalytic site on these PDE1C isozymes for both cAMP and cGMP. In summary, these findings suggest that the PDE1C gene undergoes tissue-specific alternative splicing that generates structurally and functionally diverse gene products.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Characterization of the elusive disulfide bridge forming human Hb variant: Hb Ta-Li beta83 (EF7)Gly --> Cys by electrospray mass spectrometry.

An electrospray mass spectrometric approach to the identification of a human hemoglobin (Hb) variant involving a Cys residue incorporation is presented. In Hb Ta-Li (beta83Gly --> Cys), Cys83 forms inter-molecular disulfide bridges. Routine analysis of the denatured Hb showed the presence of a minor beta chain variant whose mass apparently was 1 Da less than the expected mass difference of 46 Da for a Gly --> Cys substitution. Reduction of the globin chains with dithiothreitol gave an intense monomer with the expected mass difference for the Gly --> Cys substitution. After reprocessing the original raw data from the denatured Hb and taking into account the possibility of dimer formation, a component was revealed whose mass was consistent with a disulfide linked dimer of Ta-Li beta globins. The mutation was localized to peptide betaT10 by analysis of a tryptic digest. Tandem mass spectrometry and DNA sequencing confirmed the Gly --> Cys substitution occurred at residue 83 of the beta chain. Problems encountered in identifying the components in mixtures of monomers and dimers are discussed.

Chromatography, High Pressure Liquid↗

PubMed2004

Variants of uncertain clinical significance as a result of BRCA1/2 testing: impact of an ambiguous breast cancer risk message.

The identification of an increasing number of variants of uncertain clinical significance (VUCS) in genetic testing for hereditary breast cancer poses serious problems for genetic counseling, because no data are available about the psychosocial impact of discussing such an unclear risk message. The current study is the first to present data on how test applicants actually understand and cope with such a result if communicated by a geneticist. We compared 10 women who received a VUCS result with 34 women who carried the deleterious mutation, 37 women who did not carry the deleterious mutation or 'true negatives,' and 160 women who received a so-called inconclusive result before and after test disclosure. Women, with whom a VUCS result was discussed, reported quite a high level of comprehension of the result. In addition, compared with the pretest measures, they did not report a higher level of perceived risk (p = 0.58) and even reported a decrease in breast cancer distress (p = 0.03). They were very comparable to women who received an inconclusive result on all post-disclosure measures. Our results suggest that discussing a VUCS result in genetic counseling does not give rise for concern.

Adaptation, Psychological↗