Recalcitrant Cutaneous Warts in a Family with Inherited ICOS Deficiency

Youssefian, Leila; Saeidian, Amir Hossein; Tavasoli, Ali Reza; Kalamati, Elnaz; Naghipoor, Karim; Hozhabrpour, Amir; Mesdaghi, Mehrnaz; Saffarian, Zahra; Mahmoudi, Hamidreza; Nabavi, Mohammad; Shokri, Sima; Zeinali, Sirous; Béziat, Vivien; Casanova, Jean‐Laurent; Jouanguy, Emmanuelle; Uitto, Jouni; Vahidnezhad, Hassan

doi:10.1016/j.jid.2022.02.011

Cited by 5 publications

(6 citation statements)

References 49 publications

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“…In this study, we analyzed 24 whole transcriptomes of 926 viruses, including 441 HPV subtypes, in the wart and normal-appearing skin of patients with typical EV, using our newly developed, unbiased whole-transcriptomic pipeline, VirPy ( 11 , 16 ). With this approach for cutaneous virome profiling, we found that β-HPV-14 was the predominant HPV subtype, being detected in 46% of tested samples.…”

Section: Resultsmentioning

confidence: 99%

Whole transcriptome–based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, β-, and γ-HPV infections

Saeidian

Youssefian²,

Naji

et al. 2023

JCI Insight

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Human papillomaviruses (HPVs), are DNA viruses, including ~450 types, classified into five genera (α-, β-, γ-, µ-, and 𝜈-HPV). The γand 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 in 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, on 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, nine distinct biallelic mutations in TMC6 (5), TMC8 (1), and CIB1 (3), seven being previously unreported, were detected. Additionally, 20 different HPV species, including three α-, 16 β-, and one γ-HPVs, were detected, eight of which are being reported for the first time in EV patients (β-HPV-37, -47, -80, -151, -159, α-HPV-2, -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.

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Section: Resultsmentioning

confidence: 99%

Whole transcriptome–based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, β-, and γ-HPV infections

Saeidian

Youssefian²,

Naji

et al. 2023

JCI Insight

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“…RNA‐Seq was performed as the first‐tier diagnostic approach using RNA isolated from lesional tissue and normal full‐thickness skin biopsies. The bioinformatics analysis steps for the RNA‐Seq technique are described elsewhere 14,15,16,17 . Our recently developed in‐house RNA‐Seq application is able to explore skin virome including 926 different viruses and identify underlying viral infections by next‐generation sequencing‐based detection.…”

Section: Resultsmentioning

confidence: 99%

“…The bioinformatics analysis steps for the RNA-Seq technique are described elsewhere. 14,15,16,17 The proportions of the mutant alleles of the total ATP2A2 transcripts were 39% and 18% for p.R131Q and p.N767S, respectively. These two mutations were not found in normal skin of the patient.…”

Section: Re Sultsmentioning

confidence: 98%

“…Alignment and mapping were performed by STAR-2pass (v. 2.5.3a) with the human reference genome of GRCh37/ hg19 and GENCODE V27 annotations using genome reference. 14,15 For confirmation of the pathogenic variants detected by RNA-Seq, Sanger sequencing was performed on cDNA synthesized using RNA isolated from lesional and non-lesional skin as template (Qiagen).…”

Section: Mutation Analysismentioning

confidence: 99%

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Whole‐transcriptome sequencing identifies postzygotic ATP2A2 mutations in a patient misdiagnosed with herpes zoster, confirming the diagnosis of very late‐onset segmental Darier disease

Mohaghegh

Youssefian

Galehdari

et al. 2022

Experimental Dermatology

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An 82-year-old female patient presented with a recent onset of painful skin lesions in unilateral distribution on the abdominal area following the lines of Blaschko; the initial diagnosis of Varicella-Zoster infection was made. However, because the individual lesions appeared as hyperkeratotic papules and were unresponsive to antiviral therapy, a skin biopsy was performed, which revealed hyperkeratosis, suprabasal acantholysis and dyskeratosis with corps ronds and grains, consistent with acantholytic dyskeratotic acanthoma. Since this entity has been associated with Darier disease, wholetranscriptome sequencing by RNA-Seq was performed on RNA isolated from a lesion and from adjacent normal appearing skin, and a recently developed bioinformatics pipeline that can identify both genomic sequence variants and the presence of any of 926 viruses was applied. Two pathogenic missense mutations in the ATP2A2 gene were identified in the lesional but not in normal appearing skin, and no evidence of Varicella-Zoster infection was obtained. These findings confirm the diagnosis of segmental Darier disease due to postzygotic mutations in the ATP2A2 gene, and attest to the power of a novel single-step application of RNA-Seq in providing correct diagnosis in this rare genodermatosis.

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“…25 Since then, however, only 23 patients have been diagnosed, representing less than 1% of all CVID patients with known gene defects. 26,27 ICOS deficiency is an autosomal recessive disease with an average age onset of 14 years (range from 1 month to 35 years). 26 ICOS patients have presented with a wide variety of symptoms, including recurrent bacterial and viral infections of the respiratory and digestive tract, hypogammaglobulinemia, and malignancies.…”

Section: Icos Deficiencymentioning

confidence: 99%

Inborn errors of immunity associated with defects of self‐tolerance checkpoints: The CD28 family

Rush-Kittle

Gámez-Díaz

Grimbacher

2022

Pediatric Allergy Immunology

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One of the causes of inborn errors of immunity is immune dysregulation. The inability of the immune system to regulate the extent of its activity has several deleterious effects, including autoimmunity, recurrent infections, and malignancy. In recent years, many proteins in the CD28 family -CD28, ICOS, CTLA-4, PD-1, and BTLA -have come into the focus of several research areas for their consequential role in the upregulation or downregulation of the immune response. In this review, we will discuss the structure and function of these proteins, as well as provide an overview of the clinical picture of patients with genetic defects.

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Recalcitrant Cutaneous Warts in a Family with Inherited ICOS Deficiency

Cited by 5 publications

References 49 publications

Whole transcriptome–based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, β-, and γ-HPV infections

Whole transcriptome–based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, β-, and γ-HPV infections

Whole‐transcriptome sequencing identifies postzygotic ATP2A2 mutations in a patient misdiagnosed with herpes zoster, confirming the diagnosis of very late‐onset segmental Darier disease

Inborn errors of immunity associated with defects of self‐tolerance checkpoints: The CD28 family

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