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Background: Chromatinopathies are a heterogeneous group of genetic disorders caused by pathogenic variants in genes coding for chromatin state balance proteins. Remarkably, many of these syndromes present unbalanced postnatal growth, both under‐ and over‐, although little has been described in the literature. Fetal growth measurements are common practice in pregnancy management and values within normal ranges indicate proper intrauterine growth progression; on the contrary, abnormalities in intrauterine fetal growth open the discussion of possible pathogenesis affecting growth even in the postnatal period. Methods: Among the numerous chromatinopathies, we have selected six of the most documented in the literature offering evidence about two fetal overgrowth (Sotos and Weaver syndrome) and four fetal undergrowth syndromes (Bohring Opitz, Cornelia de Lange, Floating‐Harbor, and Meier Gorlin syndrome), describing their molecular characteristics, maternal biochemical results and early pregnancy findings, prenatal ultrasound findings, and postnatal characteristics. Results/Conclusion: To date, the scarce data in the literature on prenatal findings are few and inconclusive, even though these parameters may contribute to a more rapid and accurate diagnosis, calling for a better and more detailed description of pregnancy findings. [ABSTRACT FROM AUTHOR]

The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and [PAX2.sup.+] progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans., Introduction Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder caused by defective development or functioning of hypothalamic gonadotrophin-releasing hormone-secreting (GnRH-secreting) neurons, leading to deficiency of GnRH, the master hormone [...]

Introduction: Gonadotropin-releasing hormone (GnRH) deficiency causes hypogonadotropic hypogonadism (HH), a rare genetic disorder that impairs sexual reproduction. HH can be due to defective GnRH-secreting neuron development or function and may be associated with other clinical signs in overlapping genetic syndromes. With most of the cases being idiopathic, genetics underlying HH is still largely unknown. Objective: To assess the contribution of mutated Semaphorin 3G (SEMA3G) in the onset of a syndromic form of HH, characterized by intellectual disability and facial dysmorphic features. Method: By combining homozygosity mapping with exome sequencing, we identified a novel variant in the SEMA3G gene. We then applied mouse as a model organism to examine SEMA3Gexpression and its functional requirement in vivo. Further, we applied homology modelling in silico and cell culture assays in vitro to validate the pathogenicity of the identified gene variant. Results: We found that (i) SEMA3G is expressed along the migratory route of GnRH neurons and in the developing pituitary, (ii) SEMA3G affects GnRH neuron development, but is redundant in the adult hypothalamic-pituitary-gonadal axis, and (iii) mutated SEMA3G alters binding properties in silico and in vitro to its PlexinA receptors and attenuates its effect on the migration of immortalized GnRH neurons. Conclusion: In silico, in vitro, and in vivo models revealed that SEMA3G regulates GnRH neuron migration and that its mutation affecting receptor selectivity may be responsible for the HH-related defects. [ABSTRACT FROM AUTHOR]

Monitoring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community-wide transmission with a suitable and effective sampling method would be of great support for public health response to the spreading due to asymptomatic subjects in the community.Here, we describe how using saliva samples for SARS-CoV-2 detection has allowed for a weekly surveillance of a small business company and the early detection of coronavirus disease 2019 cases.As on 23rd March, two cases were detected and investigated, and control measures were rapidly applied. [ABSTRACT FROM AUTHOR]

In mammals, fertility critically depends on the pulsatile secretion of gonadotropin-releasing hormone (GnRH) by scattered hypothalamic neurons (GnRH neurons). During development, GnRH neurons originate in the nasal placode and migrate first into the nasal compartment and then through the nasal/forebrain junction, before they reach their final position in the hypothalamus. This neurodevelopmental process, which has been extensively studied in mouse models, is regulated by a plethora of factors that might control GnRH neuron migration or survival as well as the fasciculation/targeting of the olfactory/vomeronasal axons along which the GnRH neurons migrate. Defects in GnRH neuron development or release can lead to isolated GnRH deficiency, with the underlying genetic causes still being partially unknown. Recently, semaphorins and their receptors neuropilins and plexins, a large family of molecules implicated in neuronal development and plasticity, are emerging as key regulators of GnRH neuron biology and deficiency. Specifically, semaphorins have been shown to play different roles in GnRH neuron biology by regulating migration and survival during embryonic development as well as secretion in adulthood. [ABSTRACT FROM AUTHOR]

In mammals fertility depends on timely onset and cyclic secretion of gonadotropin-releasing hormone (GnRH), secreted by scattered hypothalamic neurons (GnRH neurons). These cells originate in the nasal placode and migrate first in the nasal compartment, then through the cribriform plate and finally across the basal forebrain, before they set in their final position in the hypothalamus. This long journey is regulated by many different factors that could be mutated in neuroendocrine syndromes such as congenital hypogonadotropic hypogonadism (CHH), Kallmann Syndrome (KS) and CHARGE syndrome. Recently, semaphorins, a large family of molecules, previously discovered as axon guidance cues, are emerging as key regulators of the neuroendocrine control of GnRH neurons and are acquiring an increasing role in the etiopathogenesis of CHH and KS. Specifically, semaphorins play a multifaceted action in GnRH neuron biology: on one hand regulating their migration and survival during embryonic development and, on the other, controlling the plasticity of the median eminence (ME) in terms of its response to varying sex steroid hormone levels. In this review we will focus our attention on recent studies describing the roles of different semaphorins in the normal and pathological biology of the GnRH neuronal system.