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.

Whole-exome sequencing in patients with maturation arrest: a potential additional diagnostic tool for prevention of recurrent negative testicular sperm extraction outcomes.

Study Question: Could whole-exome sequencing (WES) be useful in clinical practice for men with maturation arrest (MA) after a first testicular sperm extraction (TESE)?

Summary Answer: WES in combination with TESE yields substantial additional information and may potentially be added as a test to predict a negative outcome of a recurrent TESE in patients with MA.

What Is Known Already: At present, the only definitive contraindications for TESE in men with non-obstructive azoospermia (NOA) are a 46,XX karyotype and microdeletions in the azoospermia factor a (AZFa) and/or AZFb regions. After a first negative TESE with MA, no test currently exists to predict a negative outcome of a recurrent TESE.

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.