Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population

Neuromuscular diseases (NMDs) include a broad range of disorders affecting muscles, nerves and neuromuscular junctions. Their overlapping phenotypes and heterogeneous genetic nature have created challenges in diagnosis which calls for the implementation of massive parallel sequencing as a candidate strategy to increase the diagnostic yield. In this study, total of 45 patients, mostly offspring of consanguineous marriages were examined using whole exome sequencing. Data analysis was performed to identify the most probable pathogenic rare variants in known NMD genes which led to identification of causal variants for 33 out of 45 patients (73.3%) in the following known genes: CAPN3, Col6A1, Col6A3, DMD, DYSF, FHL1, GJB1, ISPD, LAMA2, LMNA, PLEC1, RYR1, SGCA, SGCB, SYNE1, TNNT1 and 22 novel pathogenic variants were detected. Today, the advantage of whole exome sequencing in clinical diagnostic strategies of heterogeneous disorders is clear. In this cohort, a diagnostic yield of 73.3% was achieved which is quite high compared to the overall reported diagnostic yield of 25% to 50%. This could be explained by the consanguineous background of these patients and is another strong advantage of offering clinical exome sequencing in diagnostic laboratories, especially in populations with high rate of consanguinity.     

Autosomal Recessive Nonsyndromic Arrhythmogenic Right Ventricular Cardiomyopathy without Cutaneous Involvements: A Novel Mutation

The arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic disease frequently associated with desmosomal mutations, mainly attributed to dominant mutations in the Plakophilin‐2 (PKP2) gene. Naxos and Carvajal are the syndromic forms of ARVD/C due to recessive mutations. Herein, we report an autosomal recessive form of nonsyndromic ARVD/C caused by a mutation in the PKP2 gene. After examination and implementation of diagnostic modalities, the definite diagnosis of ARVD/C was confirmed by detection of ventricular tachycardia with a left bundle branch configuration and a superior axis, T‐wave inversion in right precordial leads (i.e., V1‐V3) in a 12‐lead electrocardiogram, and a right ventricle outflow tract dilatation. Neither cutaneous involvement nor other abnormalities were observed. Genetic testing was performed during which an intronic mutation of c.2577+1G>T in the PKP2 gene was observed homozygously. The c.2577+1G>T disrupts PKP2 mRNA splicing and causes a nonsyndromic form of ARVD/C.     

High-altitude adaptation in humans: from genomics to integrative physiology

About 1.2 to 33% of high-altitude populations suffer from Monge’s disease or chronic mountain sickness (CMS). Number of factors such as age, sex, and population of origin (older, male, Andean) contribute to the percentage reported from a variety of samples. It is estimated that there are around 83 million people who live at altitudes > 2500 m worldwide and are at risk for CMS. In this review, we focus on a human “experiment in nature” in various high-altitude locations in the world—namely, Andean, Tibetan, and Ethiopian populations that have lived under chronic hypoxia conditions for thousands of years. We discuss the adaptive as well as mal-adaptive changes at the genomic and physiological levels. Although different genes seem to be involved in adaptation in the three populations, we can observe convergence at genetic and signaling, as well as physiological levels. What is important is that we and others have shown that lessons learned from the genes mined at high altitude can be helpful in better understanding and treating diseases that occur at sea level. We discuss two such examples: EDNRB and SENP1 and their role in cardiac tolerance and in the polycythemic response, respectively.     

Physicochemical characterization and optimization of glycolipid biosurfactant production by a native strain of Pseudomonas aeruginosa HAK01 and its performance evaluation for the MEOR process

In this study, a glycolipid type of biosurfactant (BS) was produced, its characteristics were evaluated and several flooding tests were conducted in a micromodel to investigate its potential for enhancing oil recovery. A rhamnolipid BS producer strain was identified as a bacterium belonging to the genus Pseudomonas aeruginosa. This BS showed good stability at temperatures of 40–121 °C, pH values of 3–10 and salinity up to 10% (w/v) NaCl which is important in Microbial Enhanced Oil Recovery (MEOR). The rhamnolipid decreased the surface tension of water from 72 to 28.1 mN m⁻¹ with a critical micelle concentration of 120 ppm. Thin layer chromatography, FTIR spectroscopy, ¹H-NMR and ¹³C-NMR spectroscopy revealed the glycolipid structure of the BS. Response surface methodology was applied to optimize BS production. Several micromodel flooding tests were conducted to study the capability of the produced rhamnolipid in enhanced oil recovery for the first time. An oil recovery factor of 43% was obtained at 120 ppm of BS solution whereas the recovery factor obtained for water flooding was 16%. Contact angle measurements showed that BS solutions altered the wettability of a glass surface from oil wet to a strongly water wet state. Also the results illustrated that all BS solutions were impressive in microbial enhanced oil recovery (MEOR) and using the produced BS a considerable amount of trapped oil can be extracted due to interfacial tension reduction, wettability alteration towards water wet conditions and improving the mobility ratio.

In this study, a glycolipid type of biosurfactant (BS) was produced, its characteristics were evaluated and several flooding tests were conducted in a micromodel to investigate its potential for enhancing oil recovery.     

The (CF3C(O)NH)(C6H5CH2NH)2P(O) phosphoric triamide as a novel carrier with excellent efficiency for Cu(ii) in a liquid membrane transport system

Transport of Ag(i), Cd(ii), Co(ii), Cu(ii), Ni(ii), Pb(ii) and Zn(ii) cations across a bulk liquid membrane (BLM) containing N,N′-dibenzyl-N′′-(2,2,2-trifluoroacetyl)-phosphoric triamide (PTC) as a new carrier is studied by atomic absorption spectrometry. The results show selective and efficient transport of the copper(ii) cation from aqueous solution in the presence of the other cations. Various factors are optimized in order to obtain maximum transport efficiency. The PTC ligand is characterized by single crystal X-ray diffraction analysis, IR, NMR (¹⁹F, ³¹P, ¹H, ¹³C) and mass spectroscopy. The complex formation reaction between copper(ii) and PTC is studied by a conductometric method, which shows the 1 : 1 stoichiometry for ligand and copper(ii).

Selective transport of Cu(ii) cation in the presence of six other cations across a bulk liquid membrane containing a novel phosphoric triamide carrier is studied.     

Cushing's syndrome during pregnancy secondary to adrenal adenoma

Pregnancy rarely occurs in untreated cases of Cushing's syndrome (CS) , because most of them are infertile due to significant maternal and fetal complications during pregnancy. Diagnosis of CS may be difficult during pregnancy. Since physiological changes of pregnancy are overlapped by classical presentation and biological confirmation of CS. Therefore the high clinical suspicious is needed for diagnosis. We present a 33 years old pregnant woman with a history of chronic hypertension from 10 years ago that referred to Imam Khomeini hospital for uncontrolled hypertension, gestational diabetes and fetal tachycardia at the 30 weeks of gestation. After initial studies abdominal MRI detected a 43 x 35 x 29 mm right adrenal mass. She was treated by anti-hypertensive drugs. But at 31.5 weeks of gestational age cesarean section was performed due to severe preeclampsia. Then two weeks after delivery open right adrenalectomy was carried out without any complications and in the histopathological evaluation benign adrenocortical adenoma was reported. CS is associated with considerable fetal and maternal morbidity and mortality. Selection of treatment method is variable and it depends on gestational age. Medical and surgical approaches have been used in managing CS in pregnancy. Surgical treatment is the first choice for CS which is recommended at the second trimester and in the late pregnancy medical treatment is preferred.     

A survey on relative frequency of metabolic syndrome and testosterone deficiency in men with erectile dysfunction

Purpose

Erectile dysfunction (ED) is a common male sexual dysfunction and affects the individual??s physical and psychological well-being. It has been classified as organic and psychogenic. Men with low testosterone levels have an increased risk of ED. On the other hand, direct detrimental effect of metabolic syndrome on the endothelium, smooth muscle and nerves of the vascular system of the penis is what causes ED to develop in men with metabolic syndrome. Therefore, it is supposed that a large number of men with erectile dysfunction are patients who have ED, metabolic syndrome and testosterone deficiency as a triad. The aim of this study is determining relative frequencies of metabolic syndrome and testosterone deficiency in a group of men with ED.

Methods

Men suffering from ED who were referred to a certain private urology clinic between 22.11.2009 and 22.9.2010 were evaluated for metabolic syndrome criteria; their morning free testosterone levels were measured, and then the related questionnaires were filled out.

Results

Of 241 men with ED, the relative frequency of metabolic syndrome was 41.5%, of testosterone deficiency was 36.5% and of metabolic syndrome in combination with testosterone deficiency was 19.5%.

Conclusion

The relative frequencies of metabolic syndrome and testosterone deficiency in men with ED seem to be significant, and it is the time that we should evaluate ED not as a disease but as a presentation of multiple underlying pathologies which needs medical attention to general health.