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Malan V.,Service dHistologie Embryologie Cytogenetique
Cytogenetic and Genome Research | Year: 2016

Cytogenetic microarray analysis is now the first-tier genetic test used in a postnatal clinical setting to explore genomic imbalances in individuals with developmental disability and/or birth defects. However, in a prenatal setting, this technique is not widely implemented, largely because the clinical impact of some copy number variants (CNVs) remains difficult to assess. This limitation is especially true in France where termination of pregnancy for medical reasons may be performed at any stage of gestation. During a period of 15 months, we investigated 382 fetuses presenting with ultrasound anomalies, using a customized microarray designed to avoid the detection of CNVs raising challenges for genetic counseling. After excluding common aneuploidies, 20/374 (5.3%) fetuses had a pathogenic CNV, among which 12/374 (3.2%) could have been detected by karyotyping, whereas 8/374 (2.1%) were cryptic. Within these 374 cases, 300 were ongoing pregnancies at the time of array comparative genomic hybridization (aCGH) testing. For these pregnancies, we detected 18/300 (6%) pathogenic CNVs, among which 6/300 (2%) were cryptic. Using this approach, only 2/300 (0.6%) of the detected CNVs raised difficulties for genetic counseling. This study confirms the added value of this strategy in a prenatal clinical setting to minimize ethical issues for genetic counseling while enhancing the detection of genomic imbalances. © 2016 S. Karger AG, Basel Copyright © 2016, S. Karger AG. All rights reserved.

Bonneau D.,French Institute of Health and Medical Research | Marlin S.,Service de Genetique | Dupont J.-M.,University of Paris Descartes | Sobol H.,Institute Paoli Calmettes | And 7 more authors.
Pathologie Biologie | Year: 2010

This article focuses on six questions raised by genetic testing in human: (1) the use of genetic tests, (2) information given to relatives of patients affected with genetic disorders, (3) prenatal and preimplantatory diagnosis for late onset genetic diseases and the use of pangenomic tests in prenatal diagnosis, (4) direct-to-consumer genetic testing, (5) population screening in the age of genomic medicine and (6) incidental findings when genetic testing are used. © 2009 Elsevier Masson SAS.

Cederroth C.R.,University of Geneva | Auger J.,Service dHistologie Embryologie | Zimmermann C.,University of Geneva | Eustache F.,Service dHistologie Embryologie Cytogenetique | Nef S.,University of Geneva
International Journal of Andrology | Year: 2010

There is growing interest in the possible health threat posed by the effects of endocrine disruptors on reproduction. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. The purpose of this review was to examine the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals. Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. However, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology. Further investigation is needed before a firm conclusion can be drawn. In the meantime, caution would suggest that perinatal phyto-oestrogen exposure, such as that found in infants feeding on soy-based formula, should be avoided. © 2009 European Academy of Andrology.

Perrin A.,University of Western Brittany | Perrin A.,French Institute of Health and Medical Research | Nguyen M.H.,University of Western Brittany | Nguyen M.H.,French Institute of Health and Medical Research | And 13 more authors.
Andrology | Year: 2013

Summary: It has been previously shown that men with chromosomal structural abnormality had a higher rate of sperm DNA fragmentation. We studied 11 male carriers of a chromosomal structural abnormality (seven with a balanced reciprocal translocation, three with a Robertsonian translocation, one with a pericentric inversion) to determine whether spermatozoa with unbalanced chromosomes were more likely to have fragmented DNA. A sequential method combining analysis of DNA fragmentation using the TUNEL assay followed by analysis of meiotic segregation by fluorescent in situ hybridization was performed on the same spermatozoa. A statistically significant higher number of spermatozoa with unbalanced chromosomal content were found to have fragmented DNA for each man. The rate of spermatozoa with DNA fragmentation was higher than the rate of those without fragmented DNA in particular modes of segregation. Our findings provide a better understanding of the mechanisms involved in male infertility ascribable to chromosomal structural abnormality. © 2013 American Society of Andrology and European Academy of Andrology.

Chafai-Elalaoui S.,Institute National dHygiene | Chafai-Elalaoui S.,Mohammed V University | Chalon M.,French National Center for Scientific Research | Elkhartoufi N.,Service dHistologie Embryologie Cytogenetique | And 11 more authors.
Journal of Medical Case Reports | Year: 2015

Introduction: Joubert syndrome is a rare congenital disorder characterized by brain malformation, developmental delay with hypotonia, ocular motor apraxia, and breathing abnormalities. Joubert syndrome is a genetically highly heterogeneous ciliopathy disorder with 23 identified causative genes. The diagnosis is based on brain imaging showing the "molar tooth sign" with cerebellar vermis agenesis. We describe a consanguineous Moroccan family with three affected siblings (18-year-old boy, 13-year-old girl, and 10-year-old boy) showing typical signs of Joubert syndrome, and attempt to identify the underlying genetic defect in this family. Methods: We performed genome-wide homozygosity mapping using a high-resolution array followed by targeted Sanger sequencing to identify the causative gene. Results: This approach found three homozygous regions, one including the AHI1 gene. Direct sequencing of the 26 coding exons of AHI1 revealed a homozygous mutation (p.Thr304AsnfsX6) located in exon 7 present in the three Joubert syndrome-affected Moroccan siblings. Of more interest, this truncating mutation was previously reported in patients with compound heterozygous Joubert syndrome originating from Spain (one patient) and from the Netherlands (two patients), suggesting a possible founder effect or mutational hotspot. Conclusions: Combined homozygosity mapping and targeted sequencing allowed the rapid detection of the disease-causing mutation in the AHI1 gene in this family affected with a highly genetically heterogeneous disorder. Carriers of the same truncating mutation (p.Thr304AsnfsX6), originating from Spain and the Netherlands, presented variable clinical characteristics, thereby corroborating the extreme heterogeneity of Joubert syndrome. © 2015 Chafai-Elalaoui et al.

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