Exploring scavenger receptor class F member 2 and the importance of scavenger receptor family in prediagnostic diseases.

Scavenger Receptor Class F Member 2 (SCARF2), also known as the Type F Scavenger Receptor Family gene, encodes for Scavenger Receptor Expressed by Endothelial Cells 2 (SREC-II). This protein is a crucial component of the scavenger receptor family and is vital in protecting mammals from infectious diseases. Although research on SCARF2 is limited, mutations in this protein have been shown to cause skeletal abnormalities in both SCARF2-deficient mice and individuals with Van den Ende-Gupta syndrome (VDEGS), which is also associated with SCARF2 mutations. In contrast, other scavenger receptors have demonstrated versatile responses and have been found to aid in pathogen elimination, lipid transportation, intracellular cargo transportation, and work in tandem with various coreceptors. This review will concentrate on recent progress in comprehending SCARF2 and the functions played by members of the Scavenger Receptor Family in pre-diagnostic diseases.

Two novel variants in SCARF2 gene underlie van den Ende-Gupta syndrome.

Van den Ende-Gupta syndrome (VDEGS) (MIM#600920) is characterized by skeletal and craniofacial abnormalities that include prominent ears, downslanting palpebral fissures, blepharophimosis, hypoplastic maxilla with or without a cleft palate, a narrow and convex nasal bridge and an everted lower lip, camptodactyly and arachnodactyly. Intelligence is normal. Recent studies have reported that patients with VDEGS have pathogenic variants in the SCARF2 gene on chromosome 22q11.21. Here, we report two Turkish patients with two novel variants [c.2291_2292insC (p.Ser765LeufsTer6) and c.488G>A (p.Cys63Tyr)] in the SCARF2 gene. In silico analysis predicted that both of these novel variants were pathogenic. To the best of our knowledge, this is the first case report of this syndrome in Turkey.

Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae as a feature of Van Den Ende-Gupta syndrome: a case report.

BACKGROUND: Van Den Ende-Gupta Syndrome (VDEGS) is an extremely rare autosomal recessive syndrome with less than 20 reported families (approximately 40 patients) in the worldwide literature. CASE PRESENTATION: We have assessed one consanguineous Saudi family with typical features of VDEGS. Two siblings were affected with almost identical features; including blepharophimosis, arachnodactyly, flexion contractures of the elbows, camptodactyly, slender ribs, hooked lateral clavicular ends, and bilateral radial head dislocations. Both patients had several unusual features; including joint laxity, flat feet, recurrent patellar dislocations, and bilateral short distal ulnae. Full sequencing of SCARF2 revealed a homozygous mutation c.773G > A (p. Cys258Tyr) in both affected children. The parents (both with no abnormalities) were heterozygous for the same mutation. CONCLUSION: Joint laxity, recurrent patellar dislocations, and short distal ulnae should be included as part of the clinical spectrum of VDEGS.

Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives.

Apela (also known as Elabela, Ende, and Toddler) is a small signaling peptide that activates the G-protein-coupled receptor Aplnr to stimulate cell migration during zebrafish gastrulation. Here, using CRISPR/Cas9 to generate a null, reporter-expressing allele, we study the role of Apela in the developing mouse embryo. We found that loss of Apela results in low-penetrance cardiovascular defects that manifest after the onset of circulation. Three-dimensional micro-computed tomography revealed a higher penetrance of vascular remodeling defects, from which some mutants recover, and identified extraembryonic anomalies as the earliest morphological distinction in Apela mutant embryos. Transcriptomics at late gastrulation identified aberrant upregulation of erythroid and myeloid markers in mutant embryos prior to the appearance of physical malformations. Double-mutant analyses showed that loss of Apela signaling impacts early Aplnr-expressing mesodermal populations independently of the alternative ligand Apelin, leading to lethal cardiac defects in some Apela null embryos.

Canine models of human rare disorders.

Millions of children worldwide are born with rare and debilitating developmental disorders each year. Although an increasing number of these conditions are being recognized at the molecular level, the characterization of the underlying pathophysiology remains a grand challenge. This is often due to the lack of appropriate patient material or relevant animal models. Dogs are coming to the rescue as physiologically relevant large animal models. Hundreds of spontaneous genetic conditions have been described in dogs, most with close counterparts to human rare disorders. Our recent examples include the canine models of human Caffey (SLC37A2), van den Ende-Gupta (SCARF2) and Raine (FAM20C) syndromes. These studies demonstrate the pathophysiological similarity of human and canine syndromes, and suggest that joint efforts to characterize both human and canine rare diseases could provide additional benefits to the advancement of the field of rare diseases. Besides revealing new candidate genes, canine models allow access to experimental resources such as cells, tissues and even live animals for research and intervention purposes.

Diagnosis of Van den Ende-Gupta syndrome: Approach to the Marden-Walker-like spectrum of disorders.

Marden-Walker syndrome is challenging to diagnose, as there is significant overlap with other multi-system congenital contracture syndromes including Beals congenital contractural arachnodactyly, D4ST1-Deficient Ehlers-Danlos syndrome (adducted thumb-clubfoot syndrome), Schwartz-Jampel syndrome, Freeman-Sheldon syndrome, Cerebro-oculo-facio-skeletal syndrome, and Van den Ende-Gupta syndrome. We discuss this differential diagnosis in the context of a boy from a consanguineous union with Van den Ende-Gupta syndrome, a diagnosis initially confused by the atypical presence of intellectual disability. SNP microarray and whole exome sequencing identified a homozygous frameshift mutation (p.L870V) in SCARF2 and predicted damaging mutations in several genes, most notably DGCR2 (p.P75L) and NCAM2 (p.S147G), both possible candidates for this child's intellectual disability. We review distinguishing features for each Marden-Walker-like syndrome and propose a clinical algorithm for diagnosis among this spectrum of disorders. © 2016 Wiley Periodicals, Inc.

Que saúde esperar ao final de uma análise? / What sort of health may be expected at the end of analysis? / Quelle santé peut-on espérer à la fin d’une analyse? / ¿Que salud se puede esperar al fin de un análisis?

Para Freud, a neurose consiste em responder aos acontecimentos da vida de forma incapacitante, diferentemente da resposta do homem sadio que os ultrapassa. Que saúde poderíamos esperar, então, ao final de uma análise? Um analista não poderia prometer mais do que a substituição da miséria neurótica pela infelicidade comum, banal, cotidiana? Freud advoga que o que se alcança por meio de uma análise não é o sintoma sexual que o sujeito apresentava ao iniciá-la, e sim sua redução a um resto incurável. A análise produz um estado que nunca surge espontaneamente no ego e que esse estado recentemente criado constitui a diferença entre uma pessoa que foi analisada e outra que não foi.

Freud defines neurosis as a way to respond to the events of life in an incorrect manner, unlike the response of the healthy man that overcomes difficulties. What form of health may we expect, then, at the end of an analysis? Can an analyst promise more than the mere replacement of neurotic misery by ordinary, banal, everyday unhappiness? Freud argues that what is achieved through an analysis is not the sexual symptom that the subject presented in the beginning, but its reduction to an incurable rest. The analysis produces a state that never arises spontaneously in the ego and this newly created state is the difference between a person who went through analysis and one who has not.

D’après Freud, la névrose consiste à répondre de façon incongrue aux vicissitudes de la vie, contrairement à la réponse de l’homme sain qui les surmonte. Qu’est-ce qui nous attend donc à la fin d’une analyse? L’analyste peut-il en effet promettre autre chose que le remplacement de la misère névrotique par le mal de vivre commun et banal de tous les jours? Freud affirme que ce qui est réalisé par le biais d’une analyse n’est pas le symptôme sexuel que le sujet présentait dès le début, mais sa réduction à un reste incurable. L’analyse produit un état qui ne se pose pas spontanément dans l’ego et cet état nouvellement créé constitue la différence entre une personne qui a été analysée et un autre qui ne l’a pas été.

Para Freud, la neurosis consiste en responder a los acontecimientos de la vida de forma dañina, contrario a la respuesta del hombre saludable que supera sus dificultades. Entonces, ¿qué salud se podría esperar al final de un análisis? ¿Podría un analista prometer más que la sustitución de la miseria neurótica, por la infelicidad cotidiana y ordinaria? Freud sostiene que lo que se logra a través de un análisis no es el síntoma sexual que el sujeto tenía al empezar, sino su reducción a un resto incurable. El análisis genera un estado que nunca surge espontáneamente en el ego y que este estado creado recientemente es la diferencia entre una persona que fue analizada y otra que no lo fue.

Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion.

Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553-559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2010] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2.

Measuring subnational under-5 mortality: lessons from a survey in the eastern Indonesian district of Ende.

There is an urgent need for measurements of the magnitude and determinants of under-5 mortality at the district level in Indonesia. This article describes a sample household survey conducted in Ende District, East Nusa Tenggara province. Complete birth histories were recorded from all women residing in a sample of 32 villages (7454 households) of Ende. The survey was conducted in early 2010, deriving measures for the period 2000-2009. The survey instrument also included key variables required to measure determinants of under-5 mortality. The results showed that there are significant differentials in under-5 mortality risk within Ende, ranging from 27 to 85 per 1000. This information will assist the district health office to implement maternal and child health programs to meet national targets for United Nations Millennium Development Goal 4. The findings provide robust mortality measures at the district level and demonstrate the feasibility of conducting such a study using local resources, in a short time, and with low costs.