Reporting a Novel Homozygous Variant in the HSD11B2 Gene: Reclassifying the Variant Using Sherloc Refinement: A Case Report Study

Background and Aim: Apparent mineralocorticoid excess (AME) is an autosomal recessive disorder resulting from a deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) caused by mutations in the HSD11B2 gene. The mutated gene affects the enzyme activity which results in the rising of cortisol that can be associated with hypokalemia, severe low-renin mineralocorticoid, hypertension, and sodium retention. Few genetic variants, almost 40, have been reported in this gene and more genetic studies are necessary. In this study, we aim to investigate an Iranian patient suspected of being affected by AME. Methods: A 2.5-year-old girl from consanguineous parents was referred to Ali Asghar Children’s Hospital. She was born prematurely with a birth weight of 2.20 kg. Her chief complaint was fever, failure to thrive, polydipsia and polyuria. The initial diagnosis was cystic fibrosis (CF), but the results of the sweat test were normal. Other differential diagnoses were apparent mineralocorticoid excess syndrome type 2, Liddle syndrome, and Bartter syndrome type2. Biochemical tests performed on the patient’s free urine showed a high ratio, almost 12, of cortisol to cortisone. Whole exome sequencing (WES) was performed to find out the causative gene. Conclusion: WES showed a novel homozygous variant in the 11βHSD2 gene. According to the American College of Medical Genetics and Genomics (ACMG) guideline, it was a vindicated uncertain significance (VUS), but using Sherloc refinement suggested that this transversion mutation is most likely to be pathogenic. *Corresponding Author: Marzieh Mojbafan; Email: [email protected]; ORCID ID: 0000-0002-9630-3561 Please cite this article as: Hozhabrpour A, Mojbafan M. Reporting a Novel Homozygous Variant in the HSD11B2 Gene: Reclassifying the Variant Using Sherloc Refinement. Arch Med Lab Sci. 2022;8:1-5 (e5). https://doi.org/10.22037/amls.v8.3937

A Systematic Review of the Possibility of Determining Age Based on DNA Methylation of the ELOVL2 Gene in Human Samples

Background: In forensic medicine, predicting the age of a victim or suspect can be a clue to solving a crime. Epigenetics has recently played a vital role in age prediction in forensic medicine. Cytosine methylation at cytosine and guanine separated by phosphate (CpG) sites is well recognized as a novel epigenetic marker for age estimation. This study aimed to summarize the information obtained from previous studies to determine age by evaluating DNA methylation in the ELOVL2 gene.Methods: In this systematic review, all related articles published between 2012 and 2022 were extracted by searching reputable scientific databases, such as ISI Web of Science, Science Direct, PubMed, and Scopus. After selecting the appropriate articles, the full text of the articles was prepared and fully evaluated by the researchers. The protocol of this study was carried out based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.Results: Out of 307 articles, 5 articles were eligible for review according to the study protocol. The strongest correlation between DNA methylation and age was observed at sites 11044644 and 11044634 on chromosome 6 in the living cases. The relationship between the chronological age and the age calculated through DNA methylation was above 90% with an approximate error ranging from 7.5 to 10.4. However, the relationship between the chronological age and the age calculated through DNA methylation was above 90% in the multivariate analysis of sites 11044624 and 11044634 on chromosome 6. In this case, the calculation error reached approximately 6.9 years. Hence, considering a combination of multiple cytosine and guanine separated by phosphate (CpG) sites improves the calculation accuracy and reduces the error percentage. The relationships between DNA methylation and the age at sites 11044880 and 11044640 on chromosome 6 were significantly less reported in the blood samples taken from the dead and in those taken from the living (nearly 64%–78.5%).Conclusion: The results of this study indicated that DNA methylation in the ELOVL2 gene could help predict a person’s biological age

Genetic diagnosis of Bartter syndrome in Iranian patients and detection of a novel homozygous CLCNKB mutation

Abstract An Iranian girl with clinical symptoms of Bartter syndrome like hypokalemia, polyuria, polydipsia, hyponatremia, and hypochloremic alkalosis was referred to us in whom the CLCNKB gene was genetically evaluated using Sanger sequencing. A homozygous pathogenic variant of c.1332_1335delCTCT was detected in this patient