AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells.

Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC. We show that AA2P-mediated HSPC expansion is driven through DNA demethylation leading to enhanced expression of AXL and GAS6. Further, we demonstrate that GAS6 enhances the serial engraftment activity of HSPCs and show that the GAS6/AXL pathway is critical for robust HSPC expansion.

Halogens engineering-based design of agonists for boosting expression of frataxin protein in Friedreich's ataxia.

OBJECTIVE: Decreased expression of the mitochondrial protein frataxin is the cause of the neurodegenerative disorder Friedreich's ataxia. In patients with cardiac disorders, the death rate of this disease is very high, up to 66%. In order to combat Friedreich ataxia, which is a potentially toxic disorder, de novo drug discovery and design have been created utilizing the approach of compound engineering with halogens. This study aimed to investigate the potential for effective treatment of Friedreich ataxia. MATERIALS AND METHODS: The screening of twenty different agonist compounds was carried out in order to find the most promising agonist compound that may be used for molecular docking prediction against the Frataxin Protein. The compound with the lowest binding energies is then optimized by halogens. The final candidate's drug-like properties are identified through Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling. Lipinski's rule of five was checked. Molecular dynamic stimulations were evaluated. RESULTS: The most potent agonist compound was identified out of twenty different compounds utilizing a docking approach against the Frataxin Protein. The compound with the lowest binding energies was next subjected to optimization by halogens. The optimized agonist 9-[1-[(1S, 5R)-8, 8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]triazol-4-yl]fluoren-9-ol  has higher binding energy of -10.4Kcal/mol with molecular weight of 705.63 g/mol. Drug-like properties are identified through ADMET profiling, having water solubility of about -7.59, skin permeation -7.08 cm/s, bioavailability score 0.17, and high GI absorption. The candidate fulfills the Lipinski rule of five and portrays efficient molecular dynamic stimulations. CONCLUSIONS: The selected agonist is one of the most potent compounds in increasing Frataxin protein expression. Furthermore, optimization with halogens can be a productive approach to improve the candidate's drug efficacy. The development of effective medications for the treatment of Friedreich ataxia would be aided by the results of these computational investigations.

A pharmacophore screening approach of homeopathic phenols for a renovated design of fragment-optimized Bauhiniastatin-1 as a drug against acromegaly.

OBJECTIVE: Acromegaly is a fatal and chronic disease that is caused by the abnormal secretion of growth hormone (GH) by the pituitary adenoma or pituitary tumor, resulting in an increased circulated concentration of insulin-like growth factors 1 (IGF-1), where in most of the cases it is secreted by a pituitary tumor. Higher levels of GH cause an increase in IGF-1 in the liver leading to multiple conditions such as cardiovascular diseases, glucose imbalance, cancer, and sleep apnea. Medical treatments such as surgery and radiotherapy can be used as the first choice of patients; however, specified human growth hormone control should be an essential treatment strategy due to an incidence rate of 0.2-1.1 yearly. Therefore, the main focus of this study is to develop a novel drug for treating acromegaly by exploiting medicinal plants that have been screened using phenol as a pharmacophore model to identify target therapeutic medicinal plant phenols. MATERIALS AND METHODS: The screening identified thirty-four pharmacophore matches of medicinal plant phenols. These were selected as suitable ligands and were docked against the growth hormone receptor to calculate their binding affinity. The candidate with the highest screened score was fragment-optimized and subjected to absorption, distribution, metabolism, and excretion (ADME) analysis, in-depth toxicity predictions, interpretation of Lipinski's rule, and molecular dynamic simulations to check the behavior of the growth hormone with the fragment-optimized candidate. RESULTS: The highest docking energy was calculated as -6.5 K/mol for Bauhiniastatin-1. Enhancing the performance of Bauhiniastatin-1 against the growth hormone receptor with fragment optimization portrayed that human growth hormone inhibition can be executed in a more efficient and better way. Fragment-optimized Bauhiniastatin-1 (FOB) was predicted with high gastrointestinal absorption, a water solubility of -2.61 as soluble, and synthetic accessibility of 4.50, achieving Lipinski's rule of 5, with low organ toxicity prediction and interpreting a positive behavior against the targeted protein. The discovery of a de novo drug candidate was confirmed by the docking of fragment-optimized Bauhiniastatin-1 (FOB), which had an energy of -4,070 Kcal/mol. CONCLUSIONS: Although successful and completely harmless, present healthcare treatment does not always eradicate the disease in some individuals. Therefore, novel formulas or combinations of currently marketed medications and emergent phytochemicals will provide new possibilities for these instances.

Revolutionizing treatment for toxic shock syndrome with engineered super chromones to combat antibiotic-resistant Staphylococcus aureus.

OBJECTIVE: Staphylococcus aureus-induced toxic shock syndrome (TSS) is a rare, but potentially fatal disease with limited treatment options. The emergence of antibiotic-resistant strains has led to a pressing need for the development of effective therapies. This study aimed to identify and optimize potential drug candidates against toxic shock syndrome by targeting the pathogenic toxin protein using chromones as lead compounds. MATERIALS AND METHODS: In this study, 20 chromones were screened for their ability to bind to the target protein. The top compounds were further optimized through the addition of cycloheptane and amide groups, and the resulting compounds were evaluated for their drug-like properties using chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. RESULTS: Among the compounds screened, 7-Glucosyloxy-5-hydroxy-2-[2-(4-hydroxyphenyl) ethyl] chromone exhibited the highest binding affinity with a molecular weight of 341.40 g/mol and a binding energy of -10.0 kcal/mol. The optimized compound exhibited favorable drug-like properties, including high water solubility, synthetic accessibility, skin permeation, bioavailability, and gastrointestinal absorption. CONCLUSIONS: This study suggests that chromones can be engineered to develop effective drugs against TSS caused by S. aureus. The optimized compound has the potential to be a promising therapeutic agent for the treatment of TSS, providing new hope for patients suffering from this life-threatening disease of toxic shock syndrome.

Higher Incidence of Unruptured Intracranial Aneurysms among Black and Hispanic Women on Screening MRA in Large Urban Populations.

BACKGROUND AND PURPOSE: Intracranial aneurysms have a reported prevalence of 1%-2% in the general population. Currently, only patients with a strong family history or autosomal dominant polycystic kidney disease are screened for intracranial aneurysms using MRA. The purpose of this study was to determine whether there are other specific patient populations at risk that should be offered screening for intracranial aneurysms. MATERIALS AND METHODS: This is a retrospective case-control study of adult patients who underwent a screening MRA of their brain at our comprehensive stroke center from 2011 to 2020. Patients with a history of a known brain aneurysm were excluded. Data were extracted on patient demographics and medical comorbidities. Bivariate analyses were performed, followed by multivariable logistic regression, to identify factors associated with a positive MRA screen for incidental aneurysms. RESULTS: Of 24,397 patients eligible for this study, 2084 screened positive for a possible intracranial aneurysm. On bivariate analysis, significant differences were present in the following categories: age, sex, race and ethnicity, chronic constipation, and hyperlipidemia. On logistic regression analysis, older age (+10 years: OR = 10.01; 95% CI, 10.01-10.02; P = .001), female sex (OR = 1.37; 95% CI, 1.24-1.51; P = .001), non-Hispanic Black (OR = 1.19; 95% CI, 1.02-1.40; P = .031), and Hispanic ethnicity (OR = 1.35; 95% CI, 1.16-1.58; P = .001) versus non-Hispanic White remained significant when adjusted for other factors. CONCLUSIONS: Targeted screening for high-risk elderly women of Black or Hispanic descent will yield higher positive findings for brain aneurysms, which may mitigate the risk of rupture. Whether this is a cost-effective approach has yet to be determined.

Readmissions in patients with cerebral cavernous malformations: a national readmission database study.

BACKGROUND: Cerebral cavernous malformations (CCMs) are microvascular CNS lesions prone to hemorrhage leading to neurological sequela such as stroke and seizure. A subset of CCM patients have aggressive disease leading to multiple bleeding events, likely resulting multiple hospitalizations. Hospital admission rates are an important metric that has direct financial impact on hospitals and an indicator of overall disease burden. Furthermore, analysis of hospital readmissions can lead to early identification of high-risk patients and provides insight into the pathogenesis of CCM lesions. The purpose of this study is to identify high risk CCM patients with increased all cause readmission and comorbidities associated with increased readmissions. METHODS: All US hospital admissions due to CCMs were searched using the 2017 National Readmission Database (NRD). Patients with readmissions within 30 days of discharge from index hospitalization were identified and analyzed, relative to the remaining population. RESULTS: Among all patients hospitalized for CCM, 14.9% (13.7-16.2%) required all cause readmission within 30 days. Multivariate logistical regression analysis showed that substance abuse (P=0.003), diabetes (P=0.018), gastrointestinal bleed (P=0.002), renal failure (P=0.027), and coronary artery disease (P=0.010) were predictive of all cause readmissions, while age group 65-74 (P=0.042), private insurance (P<0.001), and treatment at a metropolitan teaching institution (P=0.039) were protective. Approximately half of all readmissions are caused by neurological (33.9%) and infectious (14.6%) etiologies. The 30-day lesion bleeding rate after index hospitalization is 0.8% (0.5-1.2%). CONCLUSIONS: All identified comorbidities associated with increased risks of readmission contribute to vascular stress, suggesting its role in lesion pathogenesis. This is the first and only study to analyze readmission metrics for CCMs in order to identify high risk patient factors to date.

Impact of family-based selection on growth performance and immune response of Japanese quail.

The present study was aimed to evaluate the growth performance and immune response of three genetic lines of Japanese quails. These lines i.e., selected for 4-week body-weight group (WBS), selected for egg number (EBS), and random-bred control (RBC), were selected for three consecutive generations from a base population of 1125 quails. In total, 2700 four-week-old quails from three selected groups were slaughtered in total of four generations (G0 to G3). Effects of selection and generations as well as their interactions were assessed for growth performance and immune response by applying a two-way analysis of variance. Significant means were compared with Duncan's Multiple Range Test. The statistical analysis showed a significant effect of selection and generations on most of the growth and immune response parameters. WBS in G3 presented significantly higher values of body weight, weight gain, and FCR than RBC and EBS. FCR was better in WBS during G3 than those of EBS and RBC. However, Livability% was highest in RBC while the lowest was noted in G3 of WBS line. Thymus% and spleen% were higher in EBS as compared to RBC and WBS. RBC presented a better B/S ratio and ND titer than those of EBS and WBS. The decreasing trend of ND titer in both lines of WBS and EBS as compared to RBC suggested a decrease in New Castle disease resistance in progressive generations of selection. It was concluded that selection for body weight and egg number has a positive impact on respective traits but negatively affects the immunity in later generations.

Injected cells provide a valuable complement to cell-free systems for analysis of gene expression.

The aim of this short review is to comment on the advantages of injecting purified molecules into a normal living cell as a complement to the constitution of a cell-free system for analyzing the function of cell components. We emphasize here that the major difference is that, by injection, most components of a cell are maintained at their normal concentration, which is difficult, even if at all possible, to achieve in a cell-free system. We exemplify the benefits of a cell injection system by the efficiency and long duration of DNA transcription by RNA polymerase II, as used by most genes, and by the widespread success of injecting purified messenger RNA for protein synthesis. The most recent work using cell injection also gives a new understanding of a long lasting transcription factor residence on its DNA or chromatin not shown by other procedures. Lastly, we re-visit an old idea that transcription factors that guide cell fate may be stably bound to DNA or chromatin, except at S-phase or mitosis in the cell cycle, when they can undergo exchange with equivalent molecules in the cell.

Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment.

BACKGROUND: Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N-(2-fluorophenyl)-D-gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS: CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS: Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self-renewal activities of HSCs. DISCUSSION: Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.

Paracrine Factors Released by Osteoblasts Provide Strong Platelet Engraftment Properties.

Ex vivo expansion of hematopoietic stem cell (HSCs) and progenitors may one day overcome the slow platelet engraftment kinetics associated with umbilical cord blood transplantation. Serum-free medium conditioned with osteoblasts (i.e., osteoblast-conditioned medium [OCM]) derived from mesenchymal stromal cells (MSC) was previously shown to increase cell growth and raise the levels of human platelets in mice transplanted with OCM-expanded progenitors. Herein, we characterized the cellular and molecular mechanisms responsible for these osteoblast-derived properties. Limiting dilution transplantation assays revealed that osteoblasts secrete soluble factors that synergize with exogenously added cytokines to promote the production of progenitors with short-term platelet engraftment activities, and to a lesser extent with long-term platelet engraftment activities. OCM also modulated the expression repertoire of cell-surface receptors implicated in the trafficking of HSC and progenitors to the bone marrow. Furthermore, OCM contains growth factors with prosurvival and proliferation activities that synergized with stem cell factor. Insulin-like growth factor (IGF)-2 was found to be present at higher levels in OCM than in control medium conditioned with MSC. Inhibition of the IGF-1 receptor, which conveys IGF-2' intracellular signaling, largely abolished the growth-promoting activity of OCM on immature CD34+ subsets and progenitors in OCM cultures. Finally, IGF-1R effects appear to be mediated in part by the coactivator ß-catenin. In summary, these results provide new insights into the paracrine regulatory activities of osteoblasts on HSC, and how these can be used to modulate the engraftment properties of human HSC and progenitors expanded in culture. Stem Cells 2019;37:345-356.

Productive performance, egg quality, and hatching traits of Japanese quail reared under different levels of glycerin.

This study evaluated subsequent effects of glycerin on productive performance, egg quality, and hatching traits in Japanese quail. A total of 200 birds was arranged according to a completely randomized design into 5 treatment groups having 5 replicates of 8 birds each (6 females and 2 males). Treatments consisted 5 levels of glycerin, i.e., 2.5, 5, 7.5, and 10% and the control group. Birds were fed with different levels of glycerin during a rearing period of 6 wk and their subsequent effects on productive performance, egg quality, and hatching traits were observed. Data were collected regarding productive performance for 16 wk; however, egg quality and hatching traits were recorded during pre-peak (at fourth wk), peak (at 12th wk), and post peak (at 16th wk) phase. Productive performance, egg quality, and hatching traits did not differ significantly throughout the experimental period. It was concluded that glycerin can be used as a replacement energy source, having no effect on productive and reproductive performance in Japanese quail.

Distinct Molecular Signature of Murine Fetal Liver and Adult Hematopoietic Stem Cells Identify Novel Regulators of Hematopoietic Stem Cell Function.

During ontogeny, fetal liver (FL) acts as a major site for hematopoietic stem cell (HSC) maturation and expansion, whereas HSCs in the adult bone marrow (ABM) are largely quiescent. HSCs in the FL possess faster repopulation capacity as compared with ABM HSCs. However, the molecular mechanism regulating the greater self-renewal potential of FL HSCs has not yet extensively been assessed. Recently, we published RNA sequencing-based gene expression analysis on FL HSCs from 14.5-day mouse embryo (E14.5) in comparison to the ABM HSCs. We reanalyzed these data to identify key transcriptional regulators that play important roles in the expansion of HSCs during development. The comparison of FL E14.5 with ABM HSCs identified more than 1,400 differentially expressed genes. More than 200 genes were shortlisted based on the gene ontology (GO) annotation term "transcription." By morpholino-based knockdown studies in zebrafish, we assessed the function of 18 of these regulators, previously not associated with HSC proliferation. Our studies identified a previously unknown role for tdg, uhrf1, uchl5, and ncoa1 in the emergence of definitive hematopoiesis in zebrafish. In conclusion, we demonstrate that identification of genes involved in transcriptional regulation differentially expressed between expanding FL HSCs and quiescent ABM HSCs, uncovers novel regulators of HSC function.

Organic and inorganic selenium in Aseel chicken diets: Effect on hatching traits.

A study was conducted to evaluate the effect of dietary selenium (Se) sources (organic and inorganic Se at 0.30 ppm and basal diet at 0 ppm level of supplemented Se) on hatching traits in four varieties of Aseel chicken, Lakha, Mushki, Peshawari, and Mianwali. In total, 84 adult molted hens (50 wk old), 21 from each variety, were randomly assigned to 12 treatment groups in a 3 (Se diets) × 4 (Aseel varieties) factorial arrangement under a randomized complete block design. Each treatment was replicated 7 times with individual hens in each. Settable egg, fertility, hatch of fertile eggs, hatchability, A-grade chick, and embryonic mortality parameters were evaluated. The results indicated that the birds fed an organic Se supplemented diet had greater (P < 0.05) settable eggs, fertility, hatch of fertile eggs, hatchability, and A-grade chicks and reduced embryonic mortality than those fed inorganic or no Se. Among varieties, Mushki had lower (P < 0.05) fertility, hatch of fertile eggs, hatchability, and A-grade chicks than rest of three varieties. Interaction of Se sources and varieties indicated that dietary organic Se supplementation improved (P < 0.05) hatch of fertile eggs in Peshawari and Mianwali, whereas hatchability only in Peshawari variety and reduced embryonic mortality in Mianwali. It was concluded that dietary supplementation of organic Se could be used to improve hatching traits as well as reduce embryonic mortality in native Aseel chicken.

Outside-in integrin signalling regulates haematopoietic stem cell function via Periostin-Itgav axis.

Integrins play an important role in haematopoietic stem cell (HSC) maintenance in the bone marrow niche. Here, we demonstrate that Periostin (Postn) via interaction with Integrin-αv (Itgav) regulates HSC proliferation. Systemic deletion of Postn results in peripheral blood (PB) anaemia, myelomonocytosis and lymphopenia, while the number of phenotypic HSCs increases in the bone marrow. Postn-/- mice recover faster from radiation injury with concomitant loss of primitive HSCs. HSCs from Postn-/- mice show accumulation of DNA damage generally associated with aged HSCs. Itgav deletion in the haematopoietic system leads to a similar PB phenotype and HSC-intrinsic repopulation defects. Unaffected by Postn, Vav-Itgav-/- HSCs proliferate faster in vitro, illustrating the importance of Postn-Itgav interaction. Finally, the Postn-Itgav interaction inhibits the FAK/PI3K/AKT pathway in HSCs, leading to increase in p27Kip1 expression resulting in improved maintenance of quiescent HSCs. Together, we demonstrate a role for Itgav-mediated outside-in signalling in regulation of HSC proliferation and stemness.

Magnetic response of hybrid ferromagnetic and antiferromagnetic core-shell nanostructures.

The synthesis of FeTiO3-Ni(Ni80Fe20) core-shell nanostructures by a two-step method (sol-gel and DC electrodeposition) has been demonstrated. XRD analysis confirms the rhombohedral crystal structure of FeTiO3(FTO) with space group R3[combining macron]. Transmission electron microscopy clearly depicts better morphology of nanostructures with shell thicknesses of ∼25 nm. Room temperature magnetic measurements showed significant enhancement of magnetic anisotropy for the permalloy (Ni80Fe20)-FTO over Ni-FTO core-shell nanostructures. Low temperature magnetic measurements of permalloy-FeTiO3 core-shell structure indicated a strong exchange bias mechanism with magnetic coercivity below the antiferromagnetic Neel temperature (TN = 59 K). The exchange bias is attributed to the alignment of magnetic moments in the antiferromagnetic material at low temperature. Our scheme opens a path towards optimum automotive systems and wireless communications wherein broader bandwidths and smaller sizes are required.

Exchange bias in two-step artificially grown one-dimensional hybrid Co-BiFeO3 core-shell nanostructures.

One-dimensional core-shell nanostructures consisting of a ferromagnetic cobalt core and a multiferroic BiFeO3 (BFO) shell were fabricated by an artificial two-step methodology. The coupling between the ferromagnetic core and multiferroic shell manifests a significant exchange bias effect which gives a clear demonstration of the anti-ferromagnetic functionality of the BFO shell material. Exchange biases of 30 Oe and 60 Oe are observed at 300 K and at 5 K, respectively. Superparamagnetic contributions at lower temperatures play an important role in contributing to overall magnetic behavior. Dominant shape anisotropy causes parallel alignment of the easy magnetization axis along the axis of core-shell nanowires. A coherent mode of the magnetization reversal mechanism is observed by the angular dependence of coercivity (H c). This versatile two-step methodology can be employed to fabricate and investigate many other hybrid nanostructures leading to a vast scope of investigation for researchers.

Enhanced exchange bias and improved ferromagnetic properties in Permalloy-BiFe0.95Co0.05O3 core-shell nanostructures.

Hybrid core-shell nanostructures consisting of permalloy (Ni80Fe20) and multiferroic(BiFeO3, BFO/BiFe0.95Co0.05O3, BFC) materials were synthesized by a two-step method, based on wet chemical impregnation and subsequent electrodeposition within porous alumina membranes. Structural and magnetic characterizations have been done to investigate doping effect on magnetic properties and exchange bias. The magnetometry analysis revealed significant enhancements of the exchange bias and coercivity in NiFe-BFC core-shell nanostructures as compared with NiFe-BFO core-shell nanostructures. The enhancements can be attributed to the effective reduction of ferromagnet domain sizes between adjacent layers of core-shell structure. It indicates that it is possible to improve properties of multiferroic composites by site-engineering method. Our approach opens a pathway to obtain optimized nanostructured multiferroic composites exhibiting tunable magnetic properties.

Highly proliferative primitive fetal liver hematopoietic stem cells are fueled by oxidative metabolic pathways.

Hematopoietic stem cells (HSCs) in the fetal liver (FL) unlike adult bone marrow (BM) proliferate extensively, posing different metabolic demands. However, metabolic pathways responsible for the production of energy and cellular building blocks in FL HSCs have not been described. Here, we report that FL HSCs use oxygen dependent energy generating pathways significantly more than their BM counterparts. RNA-Seq analysis of E14.5 FL versus BM derived HSCs identified increased expression levels of genes involved in oxidative phosphorylation (OxPhos) and the citric acid cycle (TCA). We demonstrated that FL HSCs contain more mitochondria than BM HSCs, which resulted in increased levels of oxygen consumption and reactive oxygen species (ROS) production. Higher levels of DNA repair and antioxidant pathway gene expression may prevent ROS-mediated (geno)toxicity in FL HSCs. Thus, we here for the first time highlight the underestimated importance of oxygen dependent pathways for generating energy and building blocks in FL HSCs.

Utilizing the anti-ferromagnetic functionality of a multiferroic shell to study exchange bias in hybrid core-shell nanostructures.

A three-step method has been employed to synthesize 1D core-shell nanostructures consisting of a ferromagnetic Co90Pt10 (CoPt) core and a La doped multiferroic Bi0.87La0.13FeO3 (BLFO) shell. La doping efficiently removes the secondary impurity phases in the multiferroic shell and exchange interaction gives a significant exchange bias effect demonstrating the anti-ferromagnetic functionality of Bi0.87La0.13FeO3.

Variability of expression of oral-facial-digital syndrome type I in 15 Saudi girls: Why is there a high rate of median cleft lip in the phenotype?

BACKGROUND: It is well known that the incidence of nonsyndromal cleft lip and palate varies greatly according to ancestry: 0.3 to 0.4 per 1000 live births in blacks, one in 1000 in Caucasians, and two in 1000 in Asians and individuals from the central province of Saudi Arabia. Median cleft lip is a variable feature in oral-facial-digital syndrome type I (OFD-I). OBJECTIVE: To test the hypothesis that genetic factors may determine the lip phenotype in OFD-I patients. METHODS: A study involving 15 Saudi girls (from the central province of Saudi Arabia) with OFD-I showed a high rate (93.3%) of median cleft lip and palate. This rate in OFD-I patients is known to range from 33% to 56% in Caucasians and also known to be very low in blacks. The authors compared the rate of median cleft lip with or without cleft palate in the Arabian series (93.3%) with the rate in Caucasians and blacks. RESULTS: The difference in median cleft lip with or without cleft palate among the three groups was significant. CONCLUSION: This supports the hypothesis that ancestral genetic factors may determine the lip phenotype in OFD-I patients.

HISTORIQUE: Il est bien connu que l'incidence de fente labiale et palatine non syndromique varie considérablement selon l'ascendance : 0,3 à 0,4 cas sur 1 000 naissances vivantes chez les Noirs, un cas sur 1 000 chez les Blancs et deux cas sur 1 000 chez les Asiatiques et les personnes de la province centrale d'Arabie saoudite. La fente labiale médiane est une caractéristique variable du syndrome orofaciodigital de type I (OFD-I). OBJECTIF: Vérifier l'hypothèse selon laquelle des facteurs génétiques peuvent déterminer le phénotype labial chez des patients atteints de l'OFD-I. MÉTHODOLOGIE: Une étude auprès de 15 fillettes saoudiennes (de la province centrale d'Arabie saoudite) atteintes de l'OFD-I a révélé un taux élevé (93,3 %) de fente labiale et palatine médiane. Chez les patientes atteintes de l'OFD, on sait que ce taux varie entre 33 % et 56 % chez les Blancs et qu'il est très faible chez les Noirs. Les auteurs ont comparé le taux de fente labiale médiane accompagnée ou non d'une fente palatine dans la série de fillettes arabes (93,3 %) à celui des Blancs et des Noirs. RÉSULTATS: Dans les trois groupes, les fentes labiales médianes accompagnées ou non d'une fente palatine sont très différentes. CONCLUSION: Les résultats appuient l'hypothèse selon laquelle les facteurs génétiques liés à l'ascendance détermineraient le phénotype labial chez les patients atteints de l'OFD-I.