A RAB27A duplication in several cases of Griscelli syndrome type 2: An explanation for cases lacking a genetic diagnosis

Griscelli syndrome type 2 (GS2) is a rare and often fatal autosomal recessive, hyperinflammatory disorder. It is associated with hypopigmentation of the skin and the hair, resulting in the characteristic pigment accumulation and clumping in the hair shaft. Loss‐of‐function mutations in RAB27A, resulting from point mutations, short indel, or large deletions, account for all the cases reported to date. However, several GS2 cases originating from Saudi Arabia lack a genetic diagnosis. Here, we report on a new RAB27A genetic anomaly observed in seven Saudi Arabia families that had remained negative after extensive molecular genomic DNA testing. Linkage analysis and targeted sequencing of the RAB27A genomic region in several of these patients led to the identification of a common homozygous tandem duplication of 38 kb affecting exon 2–5 and resulting in a premature stop codon. The pathogenic effect of this duplication was confirmed by a cDNA analysis and functional assays. The identification of microhomology flanking the breakpoint site suggests a possible underlying mechanism.     

Bovine Aortic Arch in Association with Double Inlet Left Ventricle and Pulmonary Atresia: A Novel Association

We report a newborn male who was diagnosed with a double inlet left ventricle with pulmonary atresia antenatally. Postnatally, it was difficult to determine his arch anatomy echocardiographically. Therefore, he underwent three‐dimensional computed tomography angiography, which confirmed the echocardiographic findings and demonstrated a bovine aortic arch. He additionally had a single coronary artery. To our knowledge, the association of a single ventricle with a single outlet of bovine morphology is novel.     

Synonymous and non-synonymous polymorphisms in toll-like receptor 2 (TLR2) gene among complicated measles cases at a tertiary care hospital,Peshawar, Pakistan

Objectives:To detect single nucleotide polymorphism in toll-like receptor 2 (TLR2) gene in complicated cases of measles, in order to understand the genetic basis of complex human immune responses against measles complications.Methods:A total of 100 children consisted of 50 measles complicated cases while rest were gender matched disease-free individuals who served as controls for this study. Patient demographic data and clinical information were recorded on a separate pre-designed model form. All exonic regions of TLR2 gene of the patients and control samples were amplified through polymerase chain reaction. Various in-silico mutation verification tools like protein variation effect analyzer, MUPRO, sorting intolerant from tolerant, functional analysis through hidden Markov models, and polymorphism phenotyping v2 to study the effect of novel non-synonymous polymorphism on structure and function of TLR2 protein.Results:Synonymous and novel non-synonymous polymorphisms were identified in measles complicated cases. Among these, rs1816702 was marked to 5 untranslated region section of TLR2 gene, while rs3804099 and rs3804100 were identified in the coding region. Novel non-synonymous polymorphisms were shown in the coding region of TLR2 gene. No significant association was established between the observed genetic polymorphisms and measles complications. However, rs3804100 increased the risk of lower respiratory tract infection.Conclusion:The overall impact of novel non-synonymous polymorphism of TLR2 protein structure and functions was neutral and tolerated.     

The Impact of COVID-19 on Blood Transfusion Services: A Systematic Review and Meta-Analysis

IntroductionWhile SARS-CoV-2''s main transmission route is through respiratory droplets, research has found that viral RNA could be detected in blood samples, causing concerns over the safety of blood donations and blood products. This paper therefore aims to systematically search for studies that have addressed their country''s lack of donations and analyse the risk of blood transfusion-transmission. As such, it will answer the question “should blood services focus more on donation vigilance or worry more about the risks of transmission through blood products?”Methods38 articles were identified through a systematic review adopting the PRISMA and STROBE guidelines. Meta-analysis was conducted using OpenMeta software.ResultsThe average decrease in blood donations was found to be 38%, with some regions showing up to 67% decrease. To assess the risk of actual blood transfusion-transmission, three datasets were analysed. Firstly, the viral load in COVID-19 patients was studied and found to have less than 1% detection rate (ARD = −0.831, 95% −0.963, −0.699). Secondly, the prevalence of finding viral RNA in a pool of donations was nearly −1.503 (ARD = −1.538, −1.468). Lastly, recipients who were given blood products of positive donors were found to be −0.911 (ARD 95% = −1.247, −0.575).Discussion/ConclusionBlood centres should focus more on launching initiatives and policies that would increase their countries'' blood supply as the virus has no direct threat to blood safety.     

Physiologic versus anatomic repair of congenitally corrected transposition of the great arteries: meta-analysis of individual patient data

The objective of this meta-analysis of individual patients' data was to compare the immediate outcomes of anatomic and physiologic repair of congenitally corrected transposition of the great arteries. Eleven nonrandomized studies, involving 124 patients, met the inclusion criteria for this review. The Rastelli type anatomic repair and the era of surgery were significantly related to the outcome in different tested models. Entering all variables into the logistic regression model showed a significant protective effect of the Rastelli type anatomic repair (odds ratio = 0.05, 95% confidence interval: 0.01, 0.50, p = 0.02).