Publications by authors named "Devillard F"
Objective: Prenatal whole exome sequencing (pES) is increasingly prescribed for fetuses with ultrasound anomalies. Starting from the local French prenatal medicine practice, healthcare system and legal landscape, we aimed to address the broad medical and ethical issues raised by the use of pES for women and couples as well as for prenatal care providers.
Method: The French Federation of Human Genetics established a working group composed of clinicians and biologists from all over France to discuss pES challenges.
Article Synopsis
- Tatton-Brown-Rahman syndrome (TBRS) is a genetic disorder characterized by overgrowth, intellectual disability, and distinct facial features, resulting from mutations in a gene that regulates DNA methylation.* -
- A study of 24 French patients identified 17 new genetic variants, confirming that 100% showed intellectual disability, 96% had distinctive facial traits, and 87% exhibited overgrowth, alongside novel symptoms like hypertrichosis.* -
- The findings enhance the understanding of TBRS's clinical presentation, aiding in diagnosis and patient care by clarifying its genetic and phenotypic diversity.*
Article Synopsis
- * The report details a case of a 5-year-old boy with a deletion mutation in the KCNQ2 gene, diagnosed with seizures, autism, and intellectual deficiency linked to KCNQ2-encephalopathy.
- * The findings emphasize the need for genetic counseling and psychiatric evaluation to better manage the complex social and behavioral aspects of these conditions.
Article Synopsis
- Loss of function variants in CACNA1A are linked to various neurological disorders, such as episodic ataxia and developmental delays, with splicing defects being a key contributor.
- Researchers studied 11 variants of unknown significance in patients with ataxia, finding abnormal transcripts in 10 cases, eight of which were deemed harmful.
- The study confirmed the effectiveness of RNA sequencing over traditional methods, solidifying nine novel CACNA1A variants as pathogenic while suggesting flexibility in laboratory methods based on available resources.
Article Synopsis
- Reciprocal translocation (RT) carriers have a higher risk of infertility, miscarriages, and children with health issues due to the production of unbalanced gametes.
- Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) can help minimize these risks, but there are concerns about the effectiveness of sperm fluorescence in situ hybridization (spermFISH) as a diagnostic tool for RT carriers.
- A study of 41 RT carriers indicated that acrocentric chromosomes lead to more unbalanced gametes, and the variability in balanced sperm rates suggests that using spermFISH routinely may not be beneficial for these patients.
Article Synopsis
- * The study reports six new biallelic loss-of-function variations in PIEZO1, found through exome sequencing in affected fetuses and a deceased neonate from four families.
- * Most NIHF cases are identify during the second trimester, while post-mortem examinations reveal signs like ascites and pleural effusions that help in diagnosing the underlying cause.
Article Synopsis
- A recent study focuses on patients with a microduplication in the 19p13.3 region, linked to issues like growth delays, small head size, and developmental delays.
- The research analyzes a large cohort of 24 patients using advanced genomic techniques to better understand the genetic basis of this syndrome.
- The study identifies a new critical region (CR 1) associated with the duplication, which affects gene interactions critical for normal developmental processes, particularly related to head size.
Article Synopsis
- * Researchers analyzed ultrasound data from 22 fetuses with the 6qter deletion, finding significant brain abnormalities such as cerebellar hypoplasia and ventricular enlargement, alongside other structural issues.
- * The results reveal common prenatal sonographic markers for the 6q deletion syndrome and underscore the need for chromosomal microarray analysis to detect related genetic deletions in cases with observed malformations.
Article Synopsis
- Inverted duplication deletion 8p (invdupdel(8p)) is a rare genetic condition linked to developmental delays and intellectual disabilities, often presenting with brain abnormalities.
- A study analyzed 36 new cases, revealing that 97% of patients experienced developmental issues, with a significant number also suffering from seizures.
- By comparing this data with 99 previously reported cases, researchers identified a specific 5.1 Mb region in chromosome 8 associated with abnormalities of the corpus callosum, offering insights into potential genetic factors involved.
Article Synopsis
- Pathogenic variants in the MYT1L gene lead to a neurodevelopmental disorder characterized by features like developmental delays, intellectual disabilities, and behavioral disorders.
- A study analyzed genetic data from 40 previously unreported patients, adding to a total of 62 patients to better understand the clinical characteristics and genotype-phenotype correlations.
- The research confirmed key phenotypic traits, introduced new clinical features, and emphasized that patients with certain genetic variants do not show distinct clinical differences, aiding in improved diagnosis and management of the disorder.
Article Synopsis
- Nontruncating variants in the SMARCA2 gene are linked to Nicolaides-Baraitser syndrome (NCBRS), characterized by intellectual disability and congenital anomalies, but other disorders associated with SMARCA2 were unclear.
- Researchers found SMARCA2 variants in 20 individuals with syndromic neurodevelopmental disorders that did not fit the criteria for NCBRS and analyzed these variants functionally and through genetic testing.
- Results revealed a new syndrome called blepharophimosis intellectual disability syndrome (BIS), which shares some features with NCBRS but is distinct both phenotypically and at the molecular level, primarily due to the location of the SMARCA2 variants.
Article Synopsis
- The study explores the connection between impaired brain development and neurodevelopmental disorders, focusing on a rare condition called BBSOAS, caused by mutations in the NR2F1 gene.* -
- Young patients with NR2F1 mutations exhibit intellectual disabilities and specific brain malformations, which were replicated in a mouse model used by researchers to investigate the gene's function.* -
- NR2F1 is identified as a critical regulator of brain structure in both mice and humans, influencing the development of the cortex and the expression of other important development genes.*
Article Synopsis
- The text refers to a correction made to a previously published article with the DOI 10.1038/s41525-017-0035-2.
- The correction likely addresses errors or omissions in the original publication.
- This ensures that readers have access to accurate and updated information related to the research discussed in the article.
Article Synopsis
- The study examines both copy number changes in the subtelomeric 9q34 region, linked to diseases like Kleefstra syndrome (caused by the EHMT1 gene), highlighting a new patient with a small duplication of this region containing EHMT1.
- While existing patient data show that duplications of varying sizes in the 9q34 region are linked to similar neurodevelopmental disorders, the research suggests that EHMT1 may be the main contributor to these conditions.
- The findings underscore the need for larger patient studies to clarify how these genetic changes affect neurodevelopmental disorders and to better understand their cognitive and behavioral implications.
Article Synopsis
- A study investigated balanced chromosomal rearrangements in patients with intellectual disabilities and congenital anomalies using next-generation sequencing to identify breakpoints at a molecular level.
- The research characterized breakpoints in 55 patients, revealing that 89% of chromosomal rearrangements were detected, with non-homologous end-joining identified as the primary repair mechanism.
- The study found that a diagnosis could be established in about 44.8% of patients, revealing disruptions in genes and suggesting that paired-end whole genome sequencing is effective for clinical applications in structural variation analysis.
Article Synopsis
- A study of a 26-week-old male fetus with severe intrauterine growth restriction (IUGR) revealed a genetic duplication on chromosome 19 inherited from the father.
- This duplication includes the ZNF331 gene, which is normally imprinted and only expressed from the father's side in the placenta; however, in the fetus, both copies are being expressed.
- The higher expression levels of ZNF331 in the fetus's placental and renal tissues suggest a potential link between this gene and the causes of isolated IUGR, highlighting the utility of chromosomal microarray analysis (CMA) in such cases.
Article Synopsis
- Robertsonian translocations (RobT) are common chromosome rearrangements where carriers often produce mostly balanced sperm through a process called alternate segregation, raising questions about the relevance of sperm FISH analysis for these individuals.* -
- A study analyzed 23 patients from 2003-2017 alongside 187 cases from literature, finding that 73.45% of spermatozoa from RobT carriers were chromosomally balanced, in line with existing data, although some translocation types, particularly der(13;15), showed lower rates.* -
- Results suggest that despite some variations in sperm quality among RobT carriers, sperm FISH analysis remains important for genetic counseling and assessing reproductive options for these patients.*
[A specialised consultation for children and young adults with trisomy 21].
Soins Pediatr Pueric
November 2018
Article Synopsis
- The life expectancy of individuals with trisomy 21 (Down syndrome) has significantly increased, with over half living beyond 55 years today, up from just 9 years in 1929.
- This improvement is attributed to better healthcare access, enhanced medical diagnoses, and increased physical and psychological stimulation.
- Ongoing monitoring is crucial as complications can rise during puberty, yet follow-up care becomes less systematic for adolescents and adults with trisomy 21.
Article Synopsis
- * Patients commonly exhibited distinct facial characteristics that changed with age, such as midface hypoplasia and prominent ears, along with associated physical issues like hypotonia and spasticity, impacting their ability to walk.
- * Medical complications in these patients included frequent epilepsy, recurrent lung infections, and significant concerns like pulmonary hypertension leading to early mortality, highlighting the need for early screening.
Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients.
View Article and Find Full Text PDFArticle Synopsis
- Phelan-McDermid syndrome (PMS) is a genetic condition linked to deletions on chromosome 22q13, leading to symptoms like intellectual disability, speech delays, and autism spectrum disorders, with severity varying across individuals.
- The study involved analyzing 85 patients and found that 28% had abnormalities in the corpus callosum, a brain structure important for communication between hemispheres, and identified genomic regions that may contribute to specific symptoms like lack of speech.
- Additionally, researchers found significant genetic variations that might influence the severity of PMS and noted that some family members with the deletion could remain unaffected, indicating potential compensatory mechanisms for managing the disorder.
Article Synopsis
- Congenital anomalies of the kidney and urinary tract (CAKUT) are a major health issue for children, often leading to chronic kidney disease, and this study investigates the genetic causes of CAKUT related to a specific microdeletion on chromosome 1.
- Researchers analyzed eight patients with this microdeletion, identifying a gene linked to CAKUT and finding that most had serious kidney conditions and associated developmental issues, particularly in the brain and ears.
- The study emphasizes the role of the identified gene, PBX1, in proper kidney and brain development, recommending genetic testing in cases of kidney abnormalities during pregnancy to aid in counseling and management.
Article Synopsis
- The study investigates whether duplication of the ARID1A gene is linked to a new syndrome, analyzing four patients with a specific microduplication on chromosome 1p36.11.
- Researchers used advanced techniques, including RNA sequencing and cell cycle analysis, to understand the effects of this genetic duplication on patient cells.
- Findings indicate that the patients exhibited similar symptoms, such as intellectual disability and microcephaly, with altered gene expression related to these conditions, suggesting a significant link between ARID1A gene duplication and developmental disorders.
Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates whether mutations in the DNAH1 gene affect outcomes of intracytoplasmic sperm injection (ICSI) in patients with multiple morphological abnormalities of the sperm flagella (MMAF).
- Findings indicate that despite significant sperm abnormalities, MMAF patients with DNAH1 mutations exhibit low aneuploidy rates and good nuclear quality, resulting in high embryonic development success and pregnancy rates after ICSI.
- This retrospective cohort study analyzed data from 6 MMAF patients with DNAH1 mutations compared to two control groups, demonstrating that genetic factors can influence ICSI efficacy in men with sperm morphology defects.