Treatment with K6PC-5, a selective stimulator of SPHK1, ameliorates intestinal homeostasis in an animal model of Huntington's disease.

Emerging evidence indicates that Huntington's disease (HD) may be described as multi-organ pathology. In this context, we and others have contributed to demonstrate that the disease is characterized by an impairment of the homeostasis of gastro-intestinal (GI) tract. Sphingolipids represent a class of molecules involved in the regulation and maintenance of different tissues and organs including GI system. In this study, we investigated whether the alteration of Sphingosine-1-phosphate (S1P) metabolism, previously described in human HD brains and animal models, is also detectable peripherally in R6/2 HD mice. Our findings indicate, for the first time, that sphingolipid metabolism is perturbed early in the disease in the intestinal tract of HD mice and, its modulation by K6PC-5, a selective activator of S1P synthesis, preserved intestinal integrity and homeostasis. These results further support the evidence that modulation of sphingolipid pathways may represent a potential therapeutic option in HD and suggest that it has also the potential to counteract the peripheral disturbances which may usually complicate the management of the disease and affect patient's quality of life.

Altered miR-193a-5p expression in children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. METHODS: Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. RESULTS: Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4+ T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. CONCLUSIONS: Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood.

Original technique for preoperative preparation of patients and intraoperative localization of parathyroid adenomas.

Surgical approach of single parathyroid adenoma treatment is turning to a less invasive surgery, allowing us to obtain better aesthetic results, reduction of duration of surgical operation, reduction of post-operative morbidity and hospital stay. Tc99m-sestaMIBI scintigraphy is mainly performed for preoperative localization of parathyroid adenomas. Our technique is instead based on the possibility to inhibit the interference of Tc99m-sestaMIBI uptake of the thyroid gland by means of the administration of Lugol's solution. Indeed, to confirm the identification and removal of the hyperfunctional parathyroid, it is accepted as adequate an ex vivo radioactivity count of the adenoma 20% or 40% greater than the value of the post-excisional background radioactivity, in association or not with intraoperative measurement of PTH. This method allows us to perform surgery with no timetable restriction, and to clearly distinguish the radioactivity of parathyroid adenoma from that of the surrounding tissues and thyroid gland.

Characterization and predicted role of the microRNA expression profile in amnion from obese pregnant women.

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. We have studied the microRNA (miRNA) expression profile in amnion from obese and control women at delivery to investigate if a specific miRNA signature is associated with obesity. The expression profile of 365 human miRNAs was evaluated with the TaqMan Array in amnion from 10 obese and 5 control (prepregnancy body mass index (BMI) >30 and <25 kg m(-2), respectively) women at delivery. Target genes and miRNA-regulated pathways were predicted by bioinformatics. Anthropometric and biochemical parameters were also measured in mothers and newborns. Seven miRNAs were expressed only in obese women (miR-422b, miR-219, miR-575, miR-523, miR-579, miR-618 and miR-659), whereas 13 miRNAs were expressed at a higher level and 12 miRNAs at a lower level in obese women than in controls. MicroRNAs significantly downregulated the neurotrophin, cancer/ErbB, mammalian target of rapamycin, insulin, adipocytokine, actin cytoskeleton and mitogen-activated protein kinase signaling pathways. In conclusion, we show that the miRNA profile is altered in amnion during obesity and hypothesize that this could affect pathways important for placental growth and function, thereby contributing to an increase in the newborn's risk of future metabolic diseases.

Cricothyrotomy performed with the Melker™ set or the QuickTrach™ kit: procedure times, learning curves and operators' preference.

BACKGROUND: Cricothyroidotomy is a surgical airway technique in which an airway device is inserted into the trachea through an incision made at the cricothyroid membrane. It is used for the management of the "difficult airways" and may be a lifesaving procedure in "can't intubate, can't oxygenate" situations. However, many healthcare professionals working in emergency settings have little of no experience with this procedure. Achievement of theoretical and practical knowledge of different cricothyrotomy techniques is therefore a fundamental prerequisite for those healthcare professionals. MATERIALS AND METHODS: In this study, 40 volunteers representative of different categories of healthcare professionals were enrolled for the theoretical and practical 1-day training course on cricothyrotomy. Two commercially available device for cricothyrotomy were used during the course, the Melker™ set, which involves the Seldinger technique, and the QuickTrach™ kit, which does not rely on the use of a guide-wire. Each participant performed a series of 5 attempts on a manikin with each kit. Procedure time was recorded, and satisfaction with the course, preference for each cricothyrotomy kit and self-rating of cricothyrotomy skills were assessed by a self-administered questionnaire. RESULTS: Mean procedure time significantly decreased from the first to the last attempt (48.7±21.9 and 27.8±13.7 seconds, respectively; p<0.0001). The Melker™ set was the most preferred, being rated as "excellent" by 62% of participants. This preference was even more pronounced among anaesthesiologists, that are more familiar with the Seldinger technique. Participants' satisfaction was high: the course was rated as "excellent" by 66.7% of attendees, the theoretical and practical knowledge achieved was rated as "very useful" by 94% of all attendees and by 100% of the anaesthesiologists. CONCLUSIONS: A systematic approach to teach healthcare professionals in the application of various devices for the management of the socalled "difficult airways" may maximize intubation success and minimize complication. The present study provides evidence for the efficacy of training courses in Emergency Departments aimed at improving theoretical and practical cricothyrotomy skills in emergency situations.

FOXN1 mutation abrogates prenatal T-cell development in humans.

BACKGROUND: The transcription factor FOXN1 is implicated in the differentiation of thymic and skin epithelial cells, and alterations in it are responsible for the Nude/SCID phenotype. During a genetic counselling programme offered to couples at risk in a community where a high frequency of mutated FOXN1 had been documented, the identification of a human FOXN1(-/-) fetus gave the unique opportunity to study T cell development in utero. RESULTS: Total blockage of CD4(+) T cell maturation and severe impairment of CD8(+) cells were documented. Evaluation of the variable-domain ß-chain (Vß) families' usage among T lymphocytes revealed that the generation of T cell receptor (TCR) diversity occurred to some extent in the FOXN1(-/-) fetus, although it was impaired compared with the control. A few non-functional CD8(+) cells, mostly bearing TCRγδ in the absence of CD3, were found. DISCUSSION: FOXN1 is crucial for in utero T cell development in humans. The identification of a limited number of CD8(+) cells suggests an extrathymic origin for these cells, implying FOXN1-independent lymphopoiesis.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot.

OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine.  The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.

Microscopic colitis, a forgotten condition: a clinical case and review of the literature.

OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).

Polychromatic flow cytometry analysis of CD34+ hematopoietic stem cells in cryopreserved early preterm human cord blood samples.

During the last decades, extended characterizations were performed of human full-term cord blood (hTCB) cells, but little information is available on human early preterm cord blood (hEPCB) hematopoietic stem cells (HSCs). In our study, we analyzed by flow cytometry 19 hEPCB and 17 hTCB samples. First, we observed that the percentage of CD34(Pos)CD45(Dim) cells was higher in hEPCB compared with hTCB and that it decreased during 16th-20th week of pregnancy. Within the CD34(Pos)CD45(Dim) population, we examined the expression of CD29, CD31, CD38, CD90, CD117, CD133, CD135, CD200, CD243, and CD338. We found that CD135 intensity and CD243(Pos) cells percentage were lower in hEPCB compared with hTCB. As to CD38, we observed that hEPCB samples were richer in undifferentiated CD34(Pos)CD45(Dim)CD38(Neg) HSCs compared with hTCB counterparts. We also compared the expression of the above-mentioned molecules in undifferentiated and committed HSCs residing in hEPCB and hTCB. In particular, although CD34(Pos)CD45(Dim)CD38(Pos) HSCs from both hEPCB and hTCB expressed relatively higher amounts of CD29, CD71, and CD135 compared with CD34(Pos)CD45(Dim)CD38(Neg) cells, a higher expression of CD31 was restricted to CD34(Pos)CD45(Dim)CD38(Pos) cells from hEPCB samples, and a higher expression of CD117 was demonstrated in CD34(Pos)CD45(Dim)CD38(Pos) cells from hTCB samples. Moreover, our data showed that CD34(Pos)CD45(Dim) cell population from hEPCB displayed higher percent of undifferentiated CD38(Neg)CD133(Pos) cells compared with hTCB samples. Finally, analyzing monocytes and lymphocytes within the two samples, we observed that T-cell percentages were higher in hTCB, whereas B-cell percentages were higher in hEPCB. We, therefore, studied the B-cell lineage maturation and found a higher percent of pro-B and pre-B cells in hEPCB compared with hTCB samples. Taken together, these results evidence the hematopoietic peculiarity of hEPCB, potentially useful for highlighting early steps of human hematolymphopoiesis as well as for developing novel strategies of stem cell-based therapy.

Search for compensation postures with videofluoromanometric investigation in dysphagic patients affected by amyotrophic lateral sclerosis.

PURPOSE: This study was undertaken to verify the effectiveness of compensatory postures, suggested on the basis of the type of dysphagia identified at videofluoromanometric (VFM) investigation to ensure safe oropharyngeal transit. MATERIALS AND METHODS: Eighty-one patients with amyotrophic lateral sclerosis (ALS) underwent speech therapy assessment and VFM investigation of the swallowing process. In the event of altered transit, penetration or aspiration of contrast material into the airways, compensation postures for correction of the swallowing disorder were suggested and verified during VFM examination. RESULTS: In 37 patients, contrast agent transport was preserved and safe; in 19, we observed penetration of the contrast agent into the laryngeal inlet without aspiration; in 24, there was aspiration (four preswallowing, eight intraswallowing, nine postswallowing, three mixed), whereas in one patient no transit was seen. Penetration without aspiration was resolved by coughing or throat clearing; aspiration was resolved in 13 patients by assuming the chin-tuck posture and in six by rotating the head; in five patients, it was not resolved. A hyperextended head posture proved to be effective to resolve lack of transit. CONCLUSIONS: By correlating morphological with functional data, VFM enables one not only to precisely characterise the dysphagic disorder but also to identify the most appropriate compensation posture for each patient and verify its effectiveness.

Hemodialysis: yesterday, today and tomorrow.

Hemodialysis was born in 1945 to treat acute renal failure, and it has progressively become a rescue therapy for patients with chronic kidney disease (CKD) stage 5, otherwise doomed to death. During the years, technological innovations have led to improved dialytic tolerance, making possible to extend the treatment to a greater number of subjects. Low- and high-flux bicarbonate dialysis are nowadays the most frequent hemodialysis techniques; hemodiafiltration with different modalities, short daily and overnight hemo-dialysis are also widespread, each of them with peculiar characteristics. A recent randomized controlled clinical trial has identified high-flux hemodialysis as the best treatment for patients with low serum levels of albumin and for diabetics in comparison to low flux dialysis. Apart from the treatment of end-stage renal disease (ESRD), hemodialysis has new and important applications, including heart failure treatment and multiple myeloma. The need to provide hemodialysis patients a better quality of life has increased the interest in developing new techniques, such as the wearable artificial kidney, although still in initial clinical development. During the last 60 years, we have seen an exciting evolution in the field of hemodialysis, which has led to important changes in the outcome of ESRD patients. The preclinical and clinical hard work ongoing in earlier stages of CKD should be able to obtain further relevant improvements and maybe avoid the need of hemodialysis itself.

Amyotrophic lateral sclerosis: sonographic evaluation of dysphagia.

PURPOSE: The authors sought to determine the role of video ultrasonography (VUS) in the diagnostic assessment of dysphagia in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Nine patients underwent simultaneous static and dynamic VUS examination and videofluoroscopy (VFS) of swallowing. RESULTS: At the static phase, VUS showed 5/9 patients had lingual atrophy. Abnormal bolus position was observed in 6/9 patients at VUS and 3/9 at VFS. Both techniques identified an inability to keep the bolus in the oral cavity in 4/9 patients. At the dynamic phase, reduced lingual movement was observed in 5/9 patients at VUS and 2/9 at VFS. Disorganised tongue movement was seen in 3/9 patients at VUS and in 2/9 at VFS. Fragmented swallowing was only visualised at VUS. Stagnation of ingested material was never visualised at VUS, whereas it was clearly depicted in 2/9 patients at VFS. CONCLUSIONS: VUS can be integrated into the diagnostic protocol for evaluating swallowing in patients with ALS, as it has higher sensitivity than VFS in assessing the dynamic factors that represent the early signs of dysphagia.

[Aldosterone and kidney damage: clinical implications]. / Aldosterone e danno renale: implicazioni cliniche.

In addition to data regarding its effects on the heart, brain and blood vessels, extensive evidence has emerged about the contribution of aldosterone to kidney damage. This has mainly been studied in the setting of experimental models of salt-sensitive hypertension but has been confirmed also in other animal models. The evidence is supported by a clear causal relationship between aldosterone infusion and development of kidney damage and its reversal after aldosterone blockade. Since 2001, clinical data have been obtained on the antiproteinuric effect of aldosterone antagonists added to ACE inhibitors or angiotensin II receptor blockers. Unfortunately, the long-term findings are still scanty, except for those obtained in two one-year studies. Altogether, this therapeutic approach appears relatively safe and effective; however, larger studies on patients with a wider range of chronic kidney disease severities and longer follow-up are needed to confirm it.

Critical role of multidimensional flow cytometry in detecting occult leptomeningeal disease in newly diagnosed aggressive B-cell lymphomas.

Among histological aggressive non-Hodgkin lymphomas (NHL), the overall risk of central nervous system (CNS) relapse is approximately 5%, a figure which is too low to offer prophylaxis to all patients. The aim of this work is to demonstrate the utility of flow cytometry (FCM) in detecting occult leptomeningeal disease in this subtype of NHL. We studied cerebrospinal fluid (CSF) involvement in 42 newly diagnosed aggressive NHL patients at risk for CNS involvement. We used multicolour FCM to detect CSF infiltrating neoplastic cells. Among the 42 patients studied, 11 had CSF involvement as detected by FCM. Of these, only four were also positive for conventional morphology (p=0.046). These results designate that FCM as the first choice technique in NHL CSF clinical cell analysis.

[The low-protein diet in chronic kidney disease: still a valid prescription?]. / La dieta ipoproteica nella nefropatia cronica: una prescrizione ancora oggi valida?

Low-protein diets were originally identified as a therapeutic tool to alleviate symptoms and signs of uremia. Their prescription, however, became common in the 1980s to reduce the rate of progression of chronic kidney disease. Since then, several studies of this nonpharmacological intervention have been published. In particular, the Modification of Diet in Renal Disease (MDRD) study, which is a cornerstone of the nephrology literature, was specifically aimed at verifying the effectiveness of low-protein diets; the results, however, were negative. Therefore, the diet issue progressively disappeared from scientific meetings and journals, and as a consequence also its use in clinical practice has diminished. The aim of this paper is to describe the state of the art of low-protein diets almost 15 years from the publication of the MDRD study.

Should we really STOP treating patients with IgA nephropathy with steroids?

IgA nephropathy (IgAN) is the most common primary glomerulonephritis all over the world. Once considered as a benign disease, today the scientific community is aware that a significant percentage of patients eventually progress to end-stage kidney disease (ESKD). The rate of progression is often very slow. Since 1980s, several therapeutic attempts have been made with steroids. Despite different molecules, doses, and lengths of treatment, the majority of uncontrolled and controlled studies found benefits in terms of proteinuria reduction and reduction of the risk of ESKD. This was obtained with reasonable safety and tolerability, especially when steroids are given at relatively low dose and for a period not exceeding 6 months. Recently, two randomized controlled trials have questioned the efficacy and safety of steroid therapy in IgAN. However, these trials have many drawbacks that are to be considered when interpreting the findings.

[Recent advances in the prevention of cardiovascular morbidity and mortality in end-stage renal disease: role of anemia, hyperparathyroidism and calcifications]. / Recenti progressi nella prevenzione di morbilità e mortalità cardiovascolari nell'uremico: ruolo dell'anemia, iperparatiroidismo e calcificazioni.

The mortality rate in patients with end-stage renal disease (ESRD) is extremely high, mainly because of the high prevalence of cardiovascular disease. In addition to traditional cardiovascular risk factors, other factors peculiar to chronic kidney disease play a role. Anemia and calcium-phosphate disorders are of particular interest, not only because they have been related to an increased risk of death but, more importantly, because they can be reversed by treatment, thereby providing the opportunity to prevent or delay the onset of cardiovascular disease. Despite a clear association between higher hemoglobin levels and better survival, data from interventional trials do not seem to show a significant positive effect of hemoglobin normalization with erythropoiesis-stimulating agents on survival and left ventricular mass in ESRD patients. Nevertheless, partial correction of anemia is still an important goal to be reached, as is also suggested by international guidelines. Disorders of calcium-phosphate metabolism have also been clearly related to increased mortality. Unlike anemia, which can be easily corrected by treatment in most cases, mineral metabolism is much less effectively treated. New agents, such as phosphate binders not containing calcium and aluminum, vitamin D analogs with lower calcemic activity, and calcimimetics, are becoming increasingly available in everyday clinical practice and are likely to allow a higher percentage of patients to achieve the recommended targets for calcium-phosphate and parathyroid hormone. Given that these molecules have only been introduced recently, clear data from interventional studies showing improved survival after adequate correction of mineral metabolism parameters are still lacking.

[Renal tubular transport and genetic hypotension]. / Trasporto renale tubulare e forme genetiche di ipotensione.

The progressive improvement of genetic research technologies has led to the identification of different genes involved in blood pressure regulation. Renal regulation systems of sodium homeostasis play a key role. Mutations capable of determining an increase or a decrease in carrier proteins function could cause not only hypotension or hypertension, but also the related metabolic symptoms and changes, and the possible response to pharmacologic treatment. Monogenic forms of hyper- or hypotension are rare, though they highlight the importance of sodium tubular transport in blood pressure adjustment.

[Genetics and arterial hypertension: monogenic forms]. / Genetica e ipertensione arteriosa: forme monogeniche.

Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. The study of genes involved in rare forms of monogenic hypertension led to the identification of pivotal pathophysiological pathways of kidney sodium and water reabsorption that can influence blood pressure values when changed. Glucocorticoid-Remediable Aldosteronism (GRA) is characterised by normal to high aldosterone levels, despite plasma renin activity suppression, and by the fact that these alterations are corrected by exogenous glucocorticoid administration. Apparent Mineralocorticoid Excess (AME) is due to a mutation of the gene encoding the renal isoform of 11 â HSD enzyme; the non-conversion of cortisol to cortisone result in increasing cortisol levels that activate the mineralocorticoid receptor. Early onset hypertension exacerbating during pregnancy is caused by a mutation leading to a conformational change in the mineralocorticoid receptor. Therefore, substances that are normally inactive at this level, such as progesterone, become potent agonists of the mutated receptor. Liddle's syndrome (or type I pseudo-hyperaldosteronism (PHA1), is characterised by a constitutive activation of the epithelial sodium channels in the distal tubule, causing an increase in sodium and chloride reabsorption. Gordon syndrome (Type II pseudo-hyperaldosteronism, PHA2) differs from the other forms because of the presence, in addition to hypertension, of hyperkaliemia and hyperchloremic acidosis that can be normalized with thiazide diuretics. Finally, a large pedigree of Turkish origin has been described: these patients are affected by an uncertain form of monogenic hypertension associated with brachydactyly.