French Guidelines of the AchroPuce Network for the Interpretation and Reporting of Constitutional Copy Number Variants.

Over the past 15 years, molecular methods for human genome analysis have evolved significantly, becoming integral to routine genetic diagnostics. Among various genomic alterations, copy-number variations (CNVs) are particularly important as sources of both benign and pathogenic variants. Accurate assessment of these variants' clinical implications is critical, especially for rare, non-recurrent CNVs and for susceptibility loci linked to neurodevelopmental disorders (NDDs).

YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse.

Purpose: Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder.

Methods: Cases with YWHAE variants were collected through international data sharing networks.

Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models.

Autism spectrum disorders (ASD) are complex conditions that stem from a combination of genetic, epigenetic and environmental influences during early pre- and postnatal childhood. The review focuses on the cerebellum and the striatum, two structures involved in motor, sensory, cognitive and social functions altered in ASD. We summarize clinical and fundamental studies highlighting the importance of these two structures in ASD.

SOX3 duplication: A genetic cause to investigate in fetuses with neural tube defects.

Objective: Neural tube defects (NTDs) are one of the most common congenital anomalies caused by a complex interaction of many genetic and environmental factors. In about 10% of cases, NTDs are associated with genetic syndromes or chromosomal anomalies. Among these, SOX3 duplication has been reported in some isolated cases.

Whole-exome sequence analysis highlights the role of unmasked recessive mutations in copy number variants with incomplete penetrance.

Several hypotheses have been proposed to explain the phenotypic variability between parent and offspring carrying the same genomic imbalance, including unmasking of a recessive variant by a chromosomal deletion. Here, 19 patients with neurodevelopmental disorders harboring a rare deletion inherited from a healthy parent were investigated by whole-exome sequencing to search for SNV on the contralateral segment. This strategy allowed us to identify a candidate variant in two patients in the NUP214 and NCOR1 genes.

Potential selection of genetically balanced spermatozoa based on the hypo-osmotic swelling test in chromosomal rearrangement carriers.

Chromosomal translocations and other balanced rearrangements, although usually associated with a normal phenotype, can lead to the transmission of an abnormal unbalanced genome to the offspring. Balanced and unbalanced spermatozoa, being indistinguishable, cannot be selected or deselected for prior to IVF and pre-implantation genetic diagnosis. Spermatozoa from 16 chromosomal rearrangement carriers were studied.

A French Approach to Test Fetuses with Ultrasound Abnormalities Using a Customized Microarray as First-Tier Genetic Test.

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.

17q21.31 microdeletion: brain anomalies leading to prenatal diagnosis.

Ultrasound examination performed on a 36-year-old woman at 33 weeks of gestation showed the presence of isolated and bilateral ventriculomegaly in the fetus. Array-based comparative genomic hybridization (array-CGH) performed on uncultured amniocytes at 35 weeks of gestation revealed a 17q21.31 microdeletion.

Translating cell-based regenerative medicines from research to successful products: challenges and solutions.

The Tissue Engineering & Regenerative Medicine International Society-Europe (TERMIS-EU) Industry Committee as well as its TERMIS-Americas (AM) counterpart intend to address the specific challenges and needs facing the industry in translating academic research into commercial products. Over the last 3 years, the TERMIS-EU Industry Committee has worked with commercial bodies to deliver programs that encourage academics to liaise with industry in proactive collaborations. The TERMIS-EU 2013 Industry Symposium aimed to build on this commercial agenda by focusing on two topics: Operations Management (How to move a process into the good manufacturing practice [GMP] environment) and Clinical Translation (Moving a GMP process into robust trials).