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

Whole Transcriptome-Based Skin Virome Profiling in Typical Epidermodysplasia Verruciformis Reveals α-, β-, and γ-HPV Infections

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, β-, γ-, μ-, and ν-HPV). The γ- and β-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of β-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to β-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 β-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (β-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV