Advantage of Whole Exome Sequencing over Allele-Specific and Targeted Segment Sequencing in Detection of Novel TULP1 Mutation in Leber Congenital Amaurosis

Background: Leber congenital amaurosis (LCA) is a severe form of retinal dystrophy with marked underlying genetic heterogeneity. Until recently, allele-specific assays and Sanger sequencing of targeted segments were the only available approaches for attempted genetic diagnosis in this condition. A broader next-generation sequencing (NGS) strategy, such as whole exome sequencing, provides an improved molecular genetic diagnostic capacity for patients with these conditions.

Materials and Methods: In a child with LCA, an allele-specific assay analyzing 135 known LCA-causing variations, followed by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and SnpEff to annotate the variants.

Results: No disease-causing variants were found using the allele-specific or targeted segment Sanger sequencing assays. Analysis of variants in the exome sequence data revealed a novel homozygous nonsense mutation (c.1081C?>?T, p.Arg361*) in TULP1, a gene with roles in photoreceptor function where mutations were previously shown to cause LCA and retinitis pigmentosa. The identified homozygous variant was the top candidate using both bioinformatic pipelines.

Conclusions: This study highlights the value of the broad sequencing strategy of exome sequencing for disease gene identification in LCA, over other existing methods. NGS is particularly beneficial in LCA where there are a large number of causative disease genes, few distinguishing clinical features for precise candidate disease gene selection, and few mutation hotspots in any of the known disease genes.     

Surveillance of injecting‐related injury and diseases in people who inject drugs attending a targeted primary health care facility in Sydney's Kings Cross

Objective: This study examined the prevalence of injecting‐related injuries and diseases (IRIDs) and associated risk factors among people who inject drugs (PWID) attending a primary health care facility in Sydney's Kings Cross. Methods: We calculated prevalence of a wide range of IRIDs utilising data reported by 702 PWID who completed a clinician‐administered survey at their first visit. Multivariable logistic regressions identified factors independently associated with at least one episode of: i) cutaneous and ii) non‐cutaneous IRIDs. Results: Lifetime prevalence of cutaneous IRIDs was 23%. Forty‐two per cent of PWID with a history of abscess attended hospital at their most recent episode. Female gender, lifetime receptive syringe sharing (RSS), injecting while in custody, and ever injecting in places other than the arm were independently associated with reporting at least one episode of cutaneous IRIDs. Ever injecting in sites other than the arm, injecting for five or more years and lifetime history of RSS were independently associated with at least one episode of non‐cutaneous IRIDs. Conclusions: IRIDs are a substantial health issue for PWID. Their ongoing surveillance is warranted particularly in primary care settings targeting PWID to inform prevention and early management, thus reducing complications that may require hospital admission.     

Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment

Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.     

A patient-reported outcome measure for patients with pituitary adenoma undergoing transsphenoidal surgery

Pituitary - Pituitary adenomas affect patients’ quality-of-life (QoL) across several domains, with long-term implications even following gross-total resection or disease remission. While...     

Selenoprotein levels in patients with colorectal adenomas and cancer

OBJECTIVES: Selenium is a trace mineral that, as a constituent of certain selenoproteins, acts as an antioxidant. Results of studies addressing a cancer protective effect of selenium have been controversial. The present study measured selenoprotein-P, extracellular glutathione peroxidase, and plasma selenium in patients with colon cancer and adenomatous colon polyps to determine whether patients who develop colorectal adenomas or cancer are selenium deficient. METHODS: Patients who presented to an endoscopy center for colonoscopy or who were referred to our institution with a newly diagnosed colorectal cancer were offered enrollment in the trial. Each patient underwent phlebotomy, usually immediately after colonoscopy. In all, 103 patients were enrolled in the study. Of these, 33 patients were found to have colorectal cancer, 35 adenomatous colon polyps, and 17 normal examinations. A total of 18 patients had other diagnoses and were not included in the study group. RESULTS: The mean age for the colorectal cancer group was 69 yr, for the adenomatous colon polyp group 62 yr, and for the normal group was 56 yr. The adenomatous colon polyp and normal groups were predominantly female. Based on one way analysis of variance tests, there was no significant difference in selenoprotein-P or plasma selenium levels or extracellular glutathione peroxidase activity among the three groups (p = 0.28, 0.098, and 0.35 respectively). CONCLUSIONS: The present data suggest that patients with adenomatous colon polyps and those with colorectal cancer are not selenium deficient.     

The Cameriere,Haavikko, Demirjian,and Willems methods for the assessment of dental age in Croatian children

International Journal of Legal Medicine - This study aimed to evaluate the accuracy and precision of the Cameriere European formula, Demirjian, Haavikko, and Willems methods for estimating dental...     

Validation of the Italian,European, North German,Malaysian, and South African black formulas on Cameriere method using panoramic radiographs in Kenyan children

International Journal of Legal Medicine - This study aimed to validate the accuracy of five different formulas based on the Cameriere method for age estimation in Kenyan children. We analyzed...