Improved variant detection using long-read sequencing and optical mapping: Illustration in STRC-related hearing loss.

Biallelic loss-of-function variants in STRC contribute to mild-moderate hearing loss (DFNB16). Here, we report a female patient with mild hearing loss. Exome sequencing and MLPA analysis revealed STRC biallelic inactivation due to a nonsense and a CKMT1B-STRC deletion.

Recurrent spontaneous pneumothorax in an NF1 patient with a novel causative variant: broadening genotype-phenotype correlations.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance, most commonly known to affect the skin and eyes. Although lung involvement in the form of cysts and bullae occurs in up to 20% of adults, the seemingly intuitive association of NF1 and spontaneous pneumothorax is not widely recognised among clinicians. Here, we report the second case of recurring spontaneous pneumothorax in the context of NF1 with a confirmed molecular diagnosis.

[Management of genetic renal disorders: local experience and importance of the network].

In nephrology, rare disorders are frequently encountered. In children, about 60% of the renal disorders are rare, with congenital abnormalities of the kidney and urinary tract disorders (CAKUT), being highly prevalent. In adults, about 22% of the disorders leading to renal replacement therapies are rare and include glomerulonephritis and genetic disorders.

Altered DNA methylation in estrogen-responsive repetitive sequences of spermatozoa of infertile men with shortened anogenital distance.

Background: It has been suggested that antenatal exposure to environmental endocrine disruptors is responsible for adverse trends in male reproductive health, including male infertility, impaired semen quality, cryptorchidism and testicular cancer, a condition known as testicular dysgenesis syndrome. Anogenital distance (AGD) is an anthropomorphic measure of antenatal exposure to endocrine disruptors, with higher exposure levels leading to shortened AGD. We hypothesized that exposure to endocrine disruptors could lead to changes in DNA methylation during early embryonic development, which could then persist in the sperm of infertile men with shortened AGD.

Increased Arterial Responsiveness to Angiotensin II in Mice Conceived by Assisted Reproductive Technologies.

Since the first report in 1978, the number of individuals conceived by Assisted Reproductive Technologies (ART) has grown incessantly. In parallel, with the recent emergence of possible underlying mechanisms of ART-induced epigenetic changes in the renin-angiotensin system, the cardiovascular repercussions of ART in mice and human offspring (including arterial hypertension, vascular dysfunction, and cardiac remodeling) have become increasingly recognized. Here, we hypothesized that ART may increase arterial responsiveness to angiotensin II (ANG II) by epigenetically modifying the expression of its receptors.

[Molecular genetic diagnosis in children with cochlear implants in the Western french speaking part of Switzerland].

Hearing loss is the most frequent sensory deficit at birth. Newborn hearing screening helps with early identification and clinical management of hearing deficits. A cochlear implantation is advised for profound hearing loss.

The relationship of maternal and child methylation of the glucocorticoid receptor NR3C1 during early childhood and subsequent child psychopathology at school-age in the context of maternal interpersonal violence-related post-traumatic stress disorder.

Introduction: Interpersonal violent (IPV) experiences when they begin in childhood and continue in various forms during adulthood often lead to chronic post-traumatic stress disorder (PTSD) that is associated in multiple studies with hypocortisolism and lower percentage of methylation of the promoter region of the gene coding for the glucocorticoid receptor (NR3C1). This prospective, longitudinal study examined the relationship of NR3C1 methylation among mothers with IPV-related PTSD and their toddlers and then looked at the relationship of maternal NR3C1 methylation and child psychopathology at school age.

Methods: Forty-eight mothers were evaluated for life-events history and post-traumatic stress disorder structured clinical interview when their children were ages 12-42 months (mean age 26.

GnRH replacement rescues cognition in Down syndrome.

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients.

Epigenomic Changes after Acupuncture Treatment in Patients Suffering from Burnout.

Introduction: The effects of acupuncture treatment in patients suffering from burnout may imply an epigenetic control mediated by DNA methylation changes. In this observational study, a genome-wide characterization of epigenetic changes in blood DNA, before and after acupuncture treatment, was performed in a cohort of 11 patients suffering from burnout.

Methods: Burnout was assessed using the Maslach Burnout Inventory (MBI) and DNA was extracted from blood samples and analyzed by Illumina EPIC BeadChip.

Genome-Wide Epigenomic Analyses in Patients With Nociceptive and Neuropathic Chronic Pain Subtypes Reveals Alterations in Methylation of Genes Involved in the Neuro-Musculoskeletal System.

Nociceptive pain involves the activation of nociceptors without damage to the nervous system, whereas neuropathic pain is related to an alteration in the central or peripheral nervous system. Chronic pain itself and the transition from acute to chronic pain may be epigenetically controlled. In this cross-sectional study, a genome-wide DNA methylation analysis was performed using the blood DNA reduced representation bisulfite sequencing (RRBS) technique.

Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss.

Purpose: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling.

Methods: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss.

Gestational trophoblastic disease in Switzerland: retrospective study of the impact of a regional reference centre.

Aims Of The Study: The European Society of Medical Oncology (ESMO) recommends that countries should have reference centres to provide adequate diagnosis and treatment of gestational trophoblastic disease. A trophoblastic disease centre in the French-speaking part of Switzerland was inaugurated in 2009. The objectives of this study were to report the activity of the centre during the last 10 years and analyse gestational trophoblastic disease outcomes.

Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients.

Bi-allelic loss-of-function variants of OTOA are a well-known cause of moderate-to-severe hearing loss. Whereas non-allelic homologous recombination-mediated deletions of the gene are well known, gene conversions to pseudogene OTOAP1 have been reported in the literature but never fully described nor their pathogenicity assessed. Here, we report two unrelated patients with moderate hearing-loss, who were compound heterozygotes for a converted allele and a deletion of OTOA.

Altered BDNF Methylation in Patients with Chronic Musculoskeletal Pain and High Biopsychosocial Complexity.

Purpose: The INTERMED instrument, which was developed to measure patient's biopsychosocial (BPS) complexity, represents a powerful diagnostic and therapeutic tool. Epigenetic changes are the interface between signals from the environment and genetic modifications, affecting gene expression, in particular, by DNA methylation of CpG dinucleotides in promotor regions of the corresponding genes. The brain-derived neurotrophic factor (BDNF) gene plays a crucial role in the central sensitization (CS) of pain.

[Trimethylaminuria : a perhaps not so uncommon case].

Patients come in consultation with a variety of complaints, some of which are unusual. We present here the case of a patient consulting for nauseating body odors for whom a diagnosis of trimethylaminuria could be found. This pathology, not very well known, may have important psychiatric and social repercussions.

LARS2-Perrault syndrome: a new case report and literature review.

Background: Perrault syndrome is a rare recessive and genetically heterogeneous disorder characterized by sensorineural hearing loss in males and females and gonadal dysgenesis in females. Mutations in seven different genes have been identified: HARS2, HSD17B4, CLLP, C10orf, ERAL1, TWNK and LARS2. To date, 19 variants have been reported in 18 individuals with LARS2-Perrault syndrome.

Case report: a 58 -year -old man with small kidneys and elevated liver enzymes.

Background: The conjunction of hepatitis and renal disease can be seen in several clinical context, including karyomegalic nephritis (KIN). Karyomegalic nephritis (KIN) is a rare genetic disease, with less than 50 cases reported, which incidence is probably underestimated. We report here an unusual case presentation of KIN with obtention of several organ biopsies and a novel mutation leading to the disease.

[Genetics of hearing disorders in children].

The majority of early hearing disorders are of genetic origin. In view of the genetic heterogeneity, high-throughput sequencing analysis of a panel of genes involved in hearing loss is the most effective and economical approach, providing a diagnostic yield of around 40 % today. The determination of a molecular diagnosis makes it possible to: i) adapt the audiological care; ii) to search for possible somatic problems associated with so-called syndromic hearing loss; (iii) to avoid unnecessary additional examinations in isolated hearing loss; (iv) to establish accurate genetic counseling for relatives, or even to provide early diagnosis; and (v) to lay the foundation for potential future molecular hearing loss therapies in selected cases.

[Genes and sex : which determination ?].

Relations between sex and genes are well understood in regards to the pathways that control sex differentiation and leading to phenotypic sex. However, the question of the role of genes in gender identity, sexual and affective orientation, or sexual function remains elusive. If the role of steroid hormones on brain development is established, their role on gender identity or sexual orientation is still hypothetical.

[Preimplantation genetic testing].

Preimplantation genetic testing avoids the transmission of monogenic diseases or structural chromosome abnormality to the offspring in fertile couples. Furthermore, it allows screening for aneuploidies (PGT-A, Preimplantation genetic testing for aneuploidy), with the aim of selecting one euploid embryo before transfer in infertile couples undergoing in vitro fertilization (IVF). Indeed, aneuploidies are frequent and explain most IVF failures and early miscarriages.

Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress.

Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.

[Intellectual disability: contribution of genetic studies to the etiological diagnosis].

The multidiscipinary care of patients with intellectual disability requires a structured and systematic etiological process. Today, advances in technology make it possible to perform diagnostic genetic analyzes that are highly contributive in this process. The CGH-array (Comparative Genomic Hybridization array) makes it possible to search for chromosomal anomalies with a very high level of resolution; high throughput sequencing can detect gene abnormalities on the whole exome or on a panel of genes.

Novel NEXMIF pathogenic variant in a boy with severe autistic features, intellectual disability, and epilepsy, and his mildly affected mother.

Intellectual disability (ID) and autism spectrum disorders are complex neurodevelopmental disorders occurring among all ethnic and socioeconomic groups. Pathogenic variants in the neurite extension and migration factor (NEXMIF) gene (formerly named KIAA2022) on the X chromosome are responsible for ID, autistic behavior, epilepsy, or dysmorphic features in males. Most affected females described had a milder phenotype or were asymptomatic obligate carriers.