A Novel Variant Causes Hereditary Spastic Paraplegia in a Consanguineous Pakistani Family.

Hereditary spastic paraplegia (HSP) is characterized by unsteady gait, motor incoordination, speech impairment, abnormal eye movement, progressive spasticity and lower limb weakness. Spastic paraplegia 75 (SPG75) results from a mutation in the gene that encodes myelin associated glycoprotein (MAG). Only a limited number of variants associated with SPG75 in families of European, Middle Eastern, North African, Turkish and Palestinian ancestry have been documented so far.

Analysis of repeat expansions in Georgian patients with Amyotrophic lateral sclerosis (ALS).

Background: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder that affects the upper and lower motor neurons. Several genetic risk factors have been identified in the past decade with a hexanucleotide repeat expansion in the gene being the most significant. However, the presence of repeat expansion has not been examined in the Transcaucasian region, therefore we aimed to analyse its frequency in Georgian patients with ALS.

Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders.

Purpose: We describe 3 families with Charcot-Marie-Tooth neuropathy (CMT), harboring a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant previously linked to fatal Leigh syndrome.

Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features.

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities.

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in -Related Disorder.

is one of four human homologs of the gene (). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.

Impact of hemorheological and endothelial factors on microcirculation.

Previous studies showed that endothelial alterations caused by physical stress worsened the hemorheological parameters mainly in patients affected by ischemic vascular diseases: major vascular alterations have been found in patients with very high endothelial dysfunction indexes: these indexes are given by the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, an endogenous vasodilator whose synthesis is catalyzed by NOs, can be determined by the Citrulline/Arginine ratio, which represents the level of activity of the enzyme. A very good index of the endothelial dysfunction is asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOs; in fact several studies have demonstrated a strong relationship between ischemic vascular disease and high levels of plasmatic ADMA.

Evaluation of a torsional-vibrating technique for the hemorheological characterization.

Clinical measurement of blood viscosity is an important parameter in the diagnosis of different diseases (e.g., diabetes, hypertension, cardiovascular diseases).

Endothelium and hemorheology.

Hemorheological alterations which can be found in ischaemic vascular diseases are well known and widely studied; less clear is the relationship between these alterations and endothelial function. Our studies showed that modifications in endothelial function caused by physical stress are associated with a worsening in hemorheological parameters mainly in patients affected by ischaemic vascular diseases: major vascular alterations have been found in patients with very high levels of plasma markers endothelial dysfunction. The control of the basal tone of the vessels is given by the complex interaction between vasoconstrictor and vasodilator endothelial factors and when this equilibrium is broken we have the endothelial dysfunction.

Posterior knee pain: primary symptom of a small non-occlusive venous clot.

A healthy 9 year old girl presented with severe posterior knee pain and a small segmental non-occlusive popliteal venous thrombosis. The case is relevant for its unique presentation and symptoms. Lack of recanalisation persisted at one year follow up.

Sn, a maize bHLH gene, modulates anthocyanin and condensed tannin pathways in Lotus corniculatus.

Anthocyanins and condensed tannins are major flavonoid end-products in higher plants. While the transactivation of anthocyanins by basic helix-loop-helix (bHLH) transcription factors is well documented, very little is known about the transregulation of the pathway to condensed tannins. The present study analyses the effect of over-expressing an Sn transgene in Lotus corniculatus, a model legume, with the aim of studying the regulation of anthocyanin and tannin end-products.

Haemorheological and endothelial-dependent alterations in heart failure after ACE inhibitor, calcium antagonist and beta blocker.

The aim of our study was to evaluate endothelium-dependent dilatation induced by an ACE-inhibitor, calcium antagonist and beta blocker in patients suffering from heart failure (NYHA class II and III). We studied 34 patients (19M, 15F, mean age 76.96+/-8.

Spontaneous echo-contrast as an in vivo indicator of rheological imbalance in dilatative cardiomyopathy.

The aim of this study was to evaluate coagulative and hemorheologic assessment in patients with dilatative cardiomyopathy with or without spontaneous echo contrast (SEC). We studied 45 patients, 35 males and 10 females (mean age 72.1 +/- 9.

High levels of human chromogranin A in umbilical cord plasma and amniotic fluid at parturition.

Objective: The human placenta is a neuroendocrine organ that produces several hypothalamic and pituitary hormones that are secreted during pregnancy and parturition into maternal and fetal circulation and amniotic fluid. Human chromogranin A (CgA) is a glycoprotein mainly localized to the adrenal medulla and released in response to several stressful events. During pregnancy, intrauterine tissues express and synthesize CgA mRNA and peptide and secret it into the biologic fluids of pregnancy, so we investigated whether maternal, umbilical, and amniotic human CgA levels are affected by the stress of parturition.

Blood viscosity and red cell morphology in subjects suffering from cirrhosis before and after treatment with S-adenosyl-L-methionine (SAM).

Alterations of fluidity of the hepatocytic membrane and of the transport related systems are the basis of the cholesteatic syndrome and favour the tissue accumulation of cytotoxic metabolites. S-Adenosyl-L-Methionine (SAM) is a natural molecule which acts as a giver of methylic groups and as an enzymatic activator in several enzymatic actions of transmethylase and of transulphuration and plays a key role in biochemical processes of hepatic cell. The aim of our study was to evaluate the effects of SAM on the restoration of the membrane fluidity and on the hepatic function in general.

Evaluation of hemorheological parameters and red cell morphology in hypertension.

The aim of our study was to evaluate hemorheological parameters in two groups of patients both suffering from essential hypertension compared with an homologous group of subjects not suffering from hypertension; the 1st group was composed of 16 patients (8 females and 8 males, mean age 65.6 +/- 16.5) suffering from essential hypertension; the 2nd one of 26 patients (8 females and 18 males, mean age 74.

Haemorheological disturbances and possibility of their correction in cerebrovascular diseases.

The presence of a hemorheological disturbance must be considered in the pathophysiological and therapeutical approach to vascular diseases, including cerebral diseases. A reduction of blood fluidity, due either to increase of hematocrit (polycythemic hyperviscosity) or of fibrinogen concentration (plasmatic hyperviscosity) or of red cell rigidity (sclerocythemic hyperviscosity) is commonly considered a condition of high risk for acute or chronic brain ischemia. So many attempts have been made for improving blood fluidity with the purpose to prevent stroke and to delay cerebral deterioration in chronic condition.

Evaluation of erythrocyte morphology as deformability index in patients suffering from vascular diseases, with or without diabetes mellitus: correlation with blood viscosity and intra-erythrocytic calcium.

The aim of our study was to evaluate the erythrocytic morphology in vascular patients, with or without diabetes, showing cell alterations correlated to blood viscosity and intra-erythrocytic calcium. We studied 108 subjects: 20 normal subjects, 58 vascular patients (25 suffering from CHD, 19 from CVD, 14 from POAD) and 30 non-insulin-dependent diabetes patients with vascular disease in metabolic compensation (13 CHD, 9 CVD, 8 POAD). Erythrocytic morphology, blood viscosity and intra-erythrocytic calcium were evaluated.

Variations of erythrocyte morphology in different pathologies.

In our study we evaluated erythrocytic morphology in different pathologies which can modify flowing red cells. We followed the methodology proposed by Zipursky which allows a three-dimensional evaluation of the red cell and a classification according to the shapes observed through the optical microscope. We studied 150 subjects: 20 normal subjects, 58 patients suffering from vascular diseases, 40 affected by diabetes (type II) (10 without and 30 with vascular diseases), 22 patients with liver disease, 5 patients with monoclonal gammopathies and 5 dehydrated patients.

[An epidemiological study on blood viscosity and intraerythrocytic calcium in a group of high-school students selected according to their family histories].

An epidemiological study was performed in a group of secondary school students selected according to their family history to assess whether changes exist in blood viscosity and intraerythrocytic calcium levels in young healthy subjects with positive family histories of arterial hypertension or cerebral and cardiac ischemic vasculopathies, compared to a control group with a negative family history of these disorders. A population of 130 secondary school students without any pathologies were subdivided into 4 groups: 1) with a positive family history of ischemic cardiopathy (ICP); with a positive family history of cerebral ictus; 3) with a family history of arterial hypertension; 4) a negative family history of these diseases. Total blood viscosity, hematocrit, plasma fibrinogen and intraerythrocytic calcium was evaluated in all groups.