Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.

Deoxyhypusine hydroxylase (DOHH) is the enzyme catalyzing the second step in the post-translational synthesis of hypusine [N-(4-amino-2-hydroxybutyl)lysine] in the eukaryotic initiation factor 5A (eIF5A). Hypusine is formed exclusively in eIF5A by two sequential enzymatic steps catalyzed by deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Hypusinated eIF5A is essential for translation and cell proliferation in eukaryotes, and all three genes encoding eIF5A, DHPS, and DOHH are highly conserved throughout eukaryotes.

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein.

Purpose: Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants.

Methods: We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

Background: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies.

Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?

Prenatal exome sequencing could be complex because of limited phenotypical data compared to postnatal/portmortem phenotype in fetuses affected by multiple congenital abnormalities (MCA). Here, we investigated limits of prenatal phenotype for ES interpretation thanks to a blindly reanalysis of postmortem ES data using prenatal data only in fetuses affected by MCA and harboring a (likely)pathogenic variant or a variant of unknown significance (VUS). Prenatal ES identified all causative variant previously reported by postmortem ES (22/24 (92%) and 2/24 (8%) using solo-ES and trio-ES respectively).

Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients.

Unique or multiple congenital facial skin polyps are features of several rare syndromes, from the most well-known Pai syndrome (PS), to the less recognized oculoauriculofrontonasal syndrome (OAFNS), encephalocraniocutaneous lipomatosis (ECCL), or Sakoda complex (SC). We set up a research project aiming to identify the molecular bases of PS. We reviewed 27 individuals presenting with a syndromic frontonasal polyp and initially referred for PS.

New horizons in Type 2 myocardial infarction: pathogenesis, assessment and management of an emerging geriatric disease.

Type 2 myocardial infarction (MI) is characterised by a functional imbalance between myocardial oxygen supply and demand in the absence of a thrombotic process, leading to myocardial necrosis. This type of MI was relatively unknown among clinicians until the third universal definition of MI was published in 2017, differentiating Type 2 from Type 1 MI, which follows an acute atherothrombotic event. The pathogenesis, diagnostic and therapeutic aspects of Type 2 MI are described in the present review.

Impact of the COVID-19 pandemic on the mental health of professionals in 77 hospitals in France.

The COVID-19 pandemic has led to significant re-organisation of healthcare delivery in hospitals, with repercussions on all professionals working in healthcare. We aimed to assess the impact of the pandemic on the mental health of professionals working in health care institutions and to identify individual and environmental factors influencing the risk of mental health disorders. From 4 June to 22 September 2020, a total of 4370 professionals responded to an online questionnaire evaluating psychological distress, severity of post-traumatic stress symptoms, stress factors, and coping strategies.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

Background: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children.

Objective: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type).

Refining the clinical phenotype associated with missense variants in exons 38 and 39 of KMT2D.

Loss-of-function variants in KMT2D are responsible for Kabuki syndrome type 1 (KS1). In the last 5 years, missense variants in exon 38 or 39 in KMT2D have been found in patients exhibiting a new phenotype with multiple malformations and absence of intellectual disability, distinct from KS1. To date, only 16 cases have been reported with classic features of hearing loss, abnormality of the ear, lacrimal duct defects, branchial sinus/neck pits, choanal atresia (CA), athelia, hypo(para)thyroidism, growth delay, and dental anomalies.

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes.

GM3 synthase deficiency in non-Amish patients.

Purpose: Biallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect.

Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype.

Purpose: Haploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS.

[The clinical practice of the psychologist in intensive care].

The intensive care psychologist was strongly mobilised during the COVID-19 health crisis. His clinical practice is both specific, with regard to the situations of extreme suffering that he is led to encounter, but also plural, as he is faced with the intersecting vulnerabilities of patients, families and carers.

[Intensive care nurse in 2021, from expertise to recognition].

The profession of intensive care nurse has been in constant evolution since the 1960s. The technical nature of medical equipment and the care of increasingly complex patients require a high level of qualification. The current health crisis has highlighted the difficulties of this profession and the lack of recognition of these carers.

Outcomes of the Composite Anterolateral Thigh Flap for Perineal Reconstruction After Postoncological Abdominoperineal Resection.

Background: The vertical rectus abdominis flap is considered the gold standard in perineal reconstruction after oncological abdominoperineal resection; however, it has a nonnegligible donor site morbidity. The anterolateral thigh flap offers reliable soft tissue coverage.

Objective: The aim was to analyze long-term outcomes of composite anterolateral thigh-vastus lateralis flaps in oncological abdominoperineal resections.

Progression-free survival on endocrine therapy, before or after chemotherapy, in hormone receptor-positive HER2-negative metastatic breast cancer.

Purpose: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era.

Methods: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres.

Hemiplegic Migraine Associated With Variations: A Clinical and Genetic Study.

Background And Objective: variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands.

Methods: was analyzed in 860 probands with hemiplegic migraine, and variations were identified in 30 probands.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

Unlabelled: The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present.

Do frozen embryo transfers modify the epigenetic control of imprinted genes and transposable elements in newborns compared with fresh embryo transfers and natural conceptions?

Objective: To determine whether the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) differs at birth between fresh or frozen embryo transfers and natural conceptions.

Design: Prospective study.

Setting: University hospital.