Genetic counselling difficulties and ethical implications of incidental findings from array-CGH: a 7-year national survey.

Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates with the whole genome, there is a risk of being confronted with incidental findings (IF). In order to anticipate the ethical issues of IF with the generalization of new genome-wide analysis technologies, we questioned French clinicians and cytogeneticists about the situations they have faced regarding IF from aCGH. Sixty-five IF were reported. Forty corresponded to autosomal dominant diseases with incomplete penetrance, 7 to autosomal dominant diseases with complete penetrance, 14 to X-linked diseases, and 4 were heterozygotes for autosomal recessive diseases with a high prevalence of heterozygotes in the population. Therapeutic/preventive measures or genetic counselling could be argued for all cases except four. These four IF were intentionally not returned to the patients. Clinicians reported difficulties in returning the results in 29% of the cases, mainly when the question of IF had not been anticipated. Indeed, at the time of the investigation, only 48% of the clinicians used consents mentioning the risk of IF. With the emergence of new technologies, there is a need to report such national experiences; they show the importance of pre-test information on IF.

Pregnancy outcomes of prenatally diagnosed Turner syndrome: a French multicenter retrospective study including a series of 975 cases.

OBJECTIVES: The objectives of this study were to report pregnancy outcomes after prenatal diagnosis of Turner syndrome (TS) and to compare and assess termination of pregnancy rates during two periods. The intervals selected were before and after 1997 when multidisciplinary centers for prenatal diagnosis (MCPDs) were established in France. METHODS: A database of 975 cases of TS diagnosed between 1980 and 2012 was created from 21 French cytogenetics laboratories. For each case, the karyotype indication, maternal age, year of prenatal testing, sampling procedure, karyotype, associated ultrasound findings, and outcomes were recorded. RESULTS: Karyotypes were mainly performed because of abnormal sonographic findings (84%). Before 1997, there were no changes in the rate of termination (90%) of affected fetuses. After 1997, the rate fell to 80%. This decrease was mainly observed in cases of mosaicism, incidental diagnosis, and in later gestations. US abnormalities were more likely to be associated with a full 45,X karyotype. CONCLUSION: There was an evolution in the way genetic counseling was performed following prenatal diagnosis of Turner syndrome that coincided with the opening of MCPDs in France. This resulted in a decrease in the rate of termination of affected fetuses.

Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.

[Is nutritional intervention influencing lipid allowances beneficial?]. / L'intervention nutritionnelle portant sur les apports lipidiques est-elle bénéfique?

An earlier study (consumption study) has shown that in subjects eating normally: 1) the amount of fat consumed per day corresponds to 4/5 of the fat contained in the portions served; 2) the distribution of the fatty acids (FA) consumed is unfavorable because of the use of saturated FA for food preparation and cooking and because of the elimination of mono- and polyunsaturated FA in the unconsumed food. In order to determine whether a simple nutritional intervention might favorably modify the distribution of FA consumed, a computer simulation of a decrease in allowances of saturated FA in exchange for an increase in mono- and polyunsaturated FA was tested. The laboratory results were compared to those of the computer program. Comparison of the intervention study with the consumption study revealed that: 1) the fat content was identical; 2) there were the same number of total calories, but there were more lipidic calories consumed during the intervention (38% instead of 35%); 3) the distribution of FA more nearly approached the recommended amounts: 40% saturated FA (-25%), 39% monounsaturated FA (+8%), 21% polyunsaturated FA (+91%) and a P/S ratio of .60 (instead of .21); 4) these proportions can be explained by a decrease in palmitic (-30%) and stearic (-20%) acids and by an increase in linoleic (+100%) and linolenic (+40%) acids; 5) the allowances of elaidic acid was on the average 4.3 g per day and had little influence on the P/S ratio; 6) the omega 6/omega 3 ratio (ratio of 7) was higher than that of the consumption study (ratio of 5); 7) there was a 16% decrease in cholesterol intake (260 mg instead of 310 mg). The laboratory findings corresponded on the whole to those of the computer program that only faulted by overestimating lipid and cholesterol allowances.

[Qualitative and quantitative assessment of lipid consumption in the intake of a community]. / Evaluation qualitative et quantitative de la consommation lipidique dans la ration d'une collectivité.

Most nutritional studies assess the nutriment allowance of a selected population from inquiries and tables of food components. Very few of them use biochemical analysis of lipid extraction, which is a more reliable process. In other respects, the investigations on the real consumption of the population are scarce. Our study aims to assess the lipid consumption of subjects submitted to normal feeding in hospital food service, from biochemical analysis of allowances and of non-consumed food. The allowances of 10 dietary days and the whole of the non-consumed food a 10 subjects by dietary day have been assessed. The results show that: 1) the ratio of fat in the non-consumed food (7.5% in wet weight) exceeds that of the proposed intake (6.6%); 2) the consumed food (1,900 KCal/d) represents 80% of the initial total calorie allowance and includes 37.5% lipid calories (71% of initial lipid allowance); 3) the distribution of the consumed fatty acids (FA) is identical to that of the fatty acids of the initial intake and not in conformity with the recommendations of the FAO/WHO Board: 53% saturated FA, 34% mononunsaturated FA, 13% polyunsaturated FA and P/S ratio: 0.23; 4) mono and polyunsaturated FA are eliminated in the non-consumed food, more particularly in unclean plates where the distribution is very near the recommended one: 48% monounsaturated FA, 21% polyunsaturated FA, 31% saturated FA and P/S ratio: 0.8; 5) in spite of these data, the consumption of essential FA remains satisfactory: 7 g of linoleic acid, and 1.5 g of linolenic acid; 6) the consumption of cholesterol (215 mg/d), corresponding to 3/4 of the initial allowance, is satisfactory. The whole of these results are correlated with the Table of Food Components and two dietary softwares.