A prevalent mutation with founder effect in Spanish Recessive Dystrophic Epidermolysis Bullosa families

Background  

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis caused by more than 500 different mutations in the COL7A1 gene and characterized by blistering of the skin following a minimal friction or mechanical trauma.     

Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

Background  

Spinal muscular atrophy (SMA) is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue.     

Sphingomyelin phosphodiesterase-1 (SMPD1) coding variants do not contribute to low levels of high-density lipoprotein cholesterol

Background  

Niemann-Pick disease type A and B is caused by a deficiency of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. In Niemann-Pick patients, SMPD1 gene defects are reported to be associated with a severe reduction in plasma high-density lipoprotein (HDL) cholesterol.     

Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans and cytokine secretion by oral epithelial cells

Background  

Oral candidiasis is a common fungal disease mainly caused by Candida albicans. The aim of this study was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on pathogenic properties of C. albicans as well as on the inflammatory response of oral epithelial cells induced by this oral pathogen.     

Search for cardiac calcium cycling gene mutations in familial ventricular arrhythmias resembling catecholaminergic polymorphic ventricular tachycardia

Background  

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited cardiac disorder caused by mutations predominantly in the ryanodine receptor (RyR2) gene. We sought to identify mutations in genes affecting cardiac calcium cycling in patients with CPVT and in less typical familial exercise-related ventricular arrhythmias.     

N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease

Background  

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.     

Mutations underlying 3-Hydroxy-3-Methylglutaryl CoA Lyase deficiency in the Saudi population

Background  

3-Hydroxy-3-Methylglutaric aciduria (3HMG, McKusick: 246450) is an autosomal recessive branched chain organic aciduria caused by deficiency of the enzyme 3-Hydroxy-3-Methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). HL is encoded by HMGCL gene and many mutations have been reported. 3HMG is commonly observed in Saudi Arabia.     

Comparative study of the antioxidant and reactive oxygen species scavenging properties in the extracts of the fruits of Terminalia chebula, Terminalia belerica and Emblica officinalis

Background  

Cellular damage caused by reactive oxygen species (ROS) has been implicated in several diseases, and hence natural antioxidants have significant importance in human health. The present study was carried out to evaluate the in vitro antioxidant and reactive oxygen species scavenging activities of Terminalia chebula, Terminalia belerica and Emblica officinalis fruit extracts.     

Rapid diagnosis of spinal muscular atrophy using High-Resolution Melting Analysis

Background  

Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disorder caused by mutations of the survival motor neuron 1 (SMN1) gene. Recently, high-resolution DNA melting analysis (HRMA) with saturation LC Green dyes has become a powerful post-PCR technique for genotyping or mutation scanning. So far, no studies have applied HRMA to the molecular analysis of SMA.     

Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

Background  

Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in post-embryonic human cells.     

A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

Background  

Familial amyloidosis with polyneuropathy (FAP) is an autosomal dominant disease caused by transthyretin (TTR) mutations, of which V30M (TTR c.148G > A, p.Val50Met, "Val30Met") is the most common. Swedish V30M carriers display later age at onset and lower penetrance compared to other populations.     

The non-syndromic familial thoracic aortic aneurysms and dissections maps to 15q21 locus

Background  

Thoracic aortic aneurysms and dissections (TAAD) is a critical condition that often goes undiagnosed with fatal consequences. While majority of the cases are sporadic, more than 20% are inherited as a single gene disorder. The most common familial TAA is Marfan syndrome (MFS), which is primarily caused by mutations in fibrillin-1 (FBN1) gene. Patients with FBN1 mutations are at higher risk for dissection compared to other patients with similar size aneurysms.     

Genomic characterization of five deletions in the LDL receptor gene in Danish Familial Hypercholesterolemic subjects

Background  

Familial Hypercholesterolemia is a common autosomal dominantly inherited disease that is most frequently caused by mutations in the gene encoding the receptor for low density lipoproteins (LDLR). Deletions and other major structural rearrangements of the LDLR gene account for approximately 5% of the mutations in many populations.     

Characterization of <Emphasis Type="Italic">n</Emphasis>-Hexane sub-fraction of <Emphasis Type="Italic">Bridelia micrantha</Emphasis> (Berth) and its antimycobacterium activity

Background  

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the most notified disease in the world. Development of resistance to first line drugs by MTB is a public health concern. As a result, there is the search for new and novel sources of antimycobacterial drugs for example from medicinal plants. In this study we determined the in vitro antimycobacterial activity of n-Hexane sub-fraction from Bridelia micrantha (Berth) against MTB H₃₇Ra and a clinical isolate resistant to all five first-line antituberculosis drugs.     

Polymorphisms of the Flavin containing monooxygenase 3 (<Emphasis Type="Italic">FMO3</Emphasis>) gene do not predispose to essential hypertension in Caucasians

Background  

The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.     

Functional characterisation of the TSC1–TSC2 complex to assess multiple <Emphasis Type="Italic">TSC2</Emphasis> variants identified in single families affected by tuberous sclerosis complex

Background  

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by seizures, mental retardation and the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR).     

Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

Background  

Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population.     

Maternal stress and hair cortisol among pregnant women following hurricane Florence

Natural disasters represent major stressors, resulting in psychological distress and physiological responses such as increased cortisol. During pregnancy, this impacts not only maternal well-being, but also fetal development. In 2018, Hurricane Florence caused extensive damage across the eastern United States. Studies indicated that compared to married pregnant women, unmarried pregnant women had higher risk of distress. Here we assess hair cortisol among a subsample of participants, and variations based on marital status.

Methods

We analyzed multiple stress measures among 37 participants who were pregnant during Hurricane Florence. We used questionnaires modeled on previous studies to assess hardship associated with the hurricane, psychological distress, sociodemographic characteristics, social support, and food security. We analyzed cortisol concentrations in proximal and distal hair sections, representing stress around the time of the disaster (distal) and 3–4 months following the disaster (proximal). We used linear regression to test relationships between hair cortisol and self-report stress measures, and variations based on marital status.

Results

Self-report measures of distress and hardship were similar among married and unmarried participants. Mean cortisol levels in distal and proximal sections were higher among unmarried participants. Controlling for confounding variables, hardship was not associated with hair cortisol. Distress predicted cortisol in distal sections (β = .482, p = .018), with a trend for proximal sections (β = .368, p = .055). Marital status was a significant predictor of distal (β = .388, p = .027) and proximal (β = .333, p = .047) hair cortisol, explaining 8.6%–11.7% of unique variance.

Conclusions

Preexisting and intersecting risk factors likely place unmarried pregnant individuals at risk of stress during and following a disaster.     

Identification of a region required for TSC1 stability by functional analysis of TSC1 missense mutations found in individuals with tuberous sclerosis complex

Background  

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Recently it has been shown that missense mutations to the TSC1 gene can cause TSC.     

New mutations in the PKD1 gene in Czech population with autosomal dominant polycystic kidney disease

Background  

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The disease is caused by mutations of the PKD1 (affecting roughly 85% of ADPKD patients) and PKD2 (affecting roughly 14% of ADPKD patients) genes, although in several ADPKD families, the PKD1 and/or PKD2 linkage was not found. Mutation analysis of the PKD1 gene is complicated by the presence of highly homologous genomic duplications of the first two thirds of the gene.