The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling.

Background: Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy-number-variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations.

Methods: Here, we report on the use of OGM in a prenatal diagnosis setting.

Stratification of the risk of ovarian dysfunction by studying the complexity of intermediate and premutation alleles of the FMR1 gene.

FMR1 premutation female carriers are at risk of developing premature/primary ovarian insufficiency (POI) with an incomplete penetrance. In this study, we determined the CGG repeat size among 1095 women with diminished ovarian reserve (DOR) / POI and characterized the CGG/AGG substructure in 44 women carrying an abnormal FMR1 repeat expansion number, compared to a group of 25 pregnant women carrying an abnormal FMR1 CGG repeat size. Allelic complexity scores of the FMR1 gene were calculated and compared between the two groups.

Next Generation Sequencing Should Be Proposed to Every Woman With "Idiopathic" Primary Ovarian Insufficiency.

Context: Primary ovarian insufficiency (POI) affects 1% of women under 40 years of age. POI is idiopathic in more than 70% of cases. Though many candidate genes have been identified in recent years, the prevalence and pathogenicity of abnormalities are still difficult to establish.

Are leptin and adiponectin involved in recurrent pregnancy loss?

Aim: The aim of this study was to investigate whether recurrent pregnancy loss (RPL) is associated with adipokine gene polymorphisms (namely the leptin -2548 (G/A), adiponectin 276 (G/T), and adiponectin 45 (T/G) polymorphisms) and/or adipokine serum levels.

Methods: A total of 145 women participated in the study. For the analysis of serum adipokine levels, 19 healthy fertile women (control group) and 60 women suffering from RPL were included.

The emerging microduplication 3q13.31: Expanding the genotype-phenotype correlations of the reciprocal microdeletion 3q13.31 syndrome.

Microdeletion and microduplication syndromes are well-known causes of developmental delay and/or malformations of differing severity. It was recently reported that a microdeletion at the 3q13.31 locus is associated with a new syndrome combining developmental delay, postnatal overgrowth and dysmorphic features.

Are de novo rea(21;21) chromosomes really de novo?

We report a rare case of recurrent trisomy 21 caused by an isochromosome 21q and what is very likely to be maternal germ-line cell mosaicism. Over 90% of cases of rob(21;21) reported in the literature are due to an isochromosome 21q, with a risk of recurrence of more than 10%.

Low-level mosaicism of a de novo derivative chromosome 9 from a t(5;9)(q35.1;q34.3) has a major phenotypic impact.

Microdeletion and microduplication syndromes are well-known causes of developmental delay and/or malformations of differing severity. Although homogeneous abnormalities can now be detected relatively easily using microarray technologies, they are more difficult to detect and interpret in cases of mosaicism. Here, we report on a male infant with a mosaic de novo derivative chromosome 9, featuring a 10.

Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies.

Objectives: The implementation of chromosomal microarray analysis (CMA) in prenatal testing for all patients has not achieved a consensus. Technical alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been applied. The aim of this study was to provide the frequencies of the submicroscopic defects detectable by PNBoBs(TM) under different prenatal indications.

Birth of a boy with isolated short stature after prenatal diagnosis of a Xp22.3 nullosomy due to an inherited t(X;15) (p22.3;p10) translocation.

Translocations between X and acrocentric chromosomes are rare. We report on the inheritance of a familial t(X;15)(p22.3;p10) translocation in a fetus referred for short long bones.

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs.

Background: A multiple pregnancy is now considered to be the most common adverse outcome associated with in vitro fertilization (IVF). As a consequence, the identification of women with the best chances of embryo implantation is a challenge in IVF program, in which the objective is to offer elective single-embryo transfer (eSET) without decreasing the pregnancy rate. To date, a range of hormonal and clinical parameters have been used to optimize eSET but none have significant predictive value.

A French collaborative survey of 272 fetuses with 22q11.2 deletion: ultrasound findings, fetal autopsies and pregnancy outcomes.

Objective: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions.

RHOXF2 gene, a new candidate gene for spermatogenesis failure.

Introduction: Genes involved in testicular differentiation, spermatogenesis, proliferation and apoptosis of germ cells have been shown to evolve rapidly and display rapid DNA changes. These genes are therefore good candidates for explaining impairments in spermatogenesis. Initial studies of some of these genes appear to confirm this hypothesis.

A genome-wide DNA methylation study in azoospermia.

The objective of this study was to assess genome-wide DNA methylation in testicular tissue from azoospermic patients. A total of 94 azoospermic patients were recruited and classified into three groups: 29 patients presented obstructive azoospermia (OA), 26 displayed non-obstructive azoospermia (NOA) and successful retrieval of spermatozoa by testicular sperm extraction (TESE+) and 39 displayed NOA and failure to retrieve spermatozoa by TESE (TESE-). An Illumina Infinium Human Methylation27 BeadChip DNA methylation array was used to establish a testicular DNA methylation pattern for each type of azoospermic patient.

Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization.

Study Question: Do TNF-308 and -238 polymorphisms impact the embryo implantation rate after in vitro fertilization (IVF) in women without female infertility factor?

Summary Answer: The presence of the TNF-308A allele is associated with high implantation and multiple pregnancy rates in women without known infertility factors after ovarian hyperstimulation with exogenous FSH.

What Is Already Known: Multiple pregnancies are frequent after the use of Assisted Reproductive Technologies. Single embryo transfer (SET) has been proposed as a simple way to prevent these risks.

Sperm FISH analysis of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat complex chromosome rearrangement.

Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother.

[What does a thorough personality questionnaire, the MMPI-2, tell us about psychological aspects of recurrent miscarriage?].

Objectives: Try to analyse the experience of couples undergoing repeated miscarriages by answering the following questions: what can we learn from these men and women who suffered from repeated miscarriages?

Patients And Methods: A thorough personality questionnaire, the MMPI-2, presented to 50 couples who have had repeated miscarriages.

Results: Through a hierarchical classification, different profiles appear in the men's group as well as in the women's group, revealing a somatization of psychological suffering. It is also revealing acute defensive personality profiles showing restricted affects in a lot of these men whose partners have suffered from multiple procreation failures.

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.

High-magnification sperm selection does not decrease the aneuploidy rate in patients who are heterozygous for reciprocal translocations.

Problem: This study sought to evaluate the value of motile sperm organelle morphology examination (MSOME) for selecting euploid spermatozoa in six patients who were heterozygous for a reciprocal translocation.

Method Of Study: We used sperm fluorescence in situ hybridization (FISH) to screen for aneuploidy of the chromosomes involved in the translocations and a putative interchromosomal effect (ICE) for chromosomes 18, X and Y. This procedure was performed on (i) whole sperm (i.

The vascular endothelial growth factor (VEGF) +405 G/C polymorphism and its relationship with recurrent implantation failure in women in an IVF programme with ICSI.

Purpose: Successful embryo implantation depends on trophoblast proliferation, migration and, lastly, invasion of the endometrium (to anchor the trophoblast to the uterus). This invasion is mediated by locally produced soluble factors. Of these, vascular endothelial growth factor (VEGF) is the best characterized regulator of angiogenesis.

Can one translocation impact the meiotic segregation of another translocation? A sperm-FISH analysis of a 46,XY,t(1;16)(q21;p11.2),t(8;9) (q24.3;p24) patient and his 46,XY,t(8;9)(q24.3;p24) brother and cousin.

Individuals with two independent chromosome rearrangements are rare and meiotic segregation studies are few. Two brothers (P1 and P2) and a cousin (P3) were karyotyped and found to have the same familial reciprocal translocation between the long arm of chromosome 8 and the short arm of chromosome 9: 46,XY,t(8;9)(q24.3;p24).

Prenatal diagnosis of the duplication 17p11.2 associated with Potocki-Lupski syndrome in a foetus presenting with mildly dysmorphic features.

Duplication 17p11.2 (Potocki-Lupski syndrome (PTLS) MIM# 610883) is a genomic disorder with an estimated incidence of 1 in 25,000 births. As for other genomic disorders this duplication is typically de novo and is not associated with advanced maternal age or advanced paternal age.