Generation of a human induced pluripotent stem cell line (UQACi001-A) from a severe epidermolysis bullosa simplex patient with the heterozygous mutation p.R125S in the KRT14 gene

We have generated UQACi001-A, a new induced pluripotent stem cell (iPSC) line derived from skin fibroblasts of a male patient with the generalized severe epidermolysis bullosa simplex phenotype (EBS-gen sev) and carrying the keratin 14 (K14) R125S mutation. Fibroblasts were reprogrammed using non-integrating Sendai virus vectors. The iPSC line displayed normal molecular karyotype, expressed pluripotency markers, is capable of differentiating into three embryonic germ layers and is genetically identical to the originating parental fibroblasts. The established iPSC model provides a valuable resource for studying the rare disease of epidermolysis bullosa simplex and developing new therapies as DNA editing by CRISPR/Cas9 technology

Generation of three induced pluripotent stem cell lines (UQACi003-A, UQACi004-A, and UQACi006-A) from three patients with KRT5 epidermolysis bullosa simplex mutations

Heterozygous mutations within Keratin 5 (KRT5) are common genetic causes of epidermolysis bullosa simplex (EBS), a skin fragility disorder characterized by blisters, which appear after minor trauma. Using CytoTune®Sendai virus, we generated three human induced pluripotent stem cell (iPSC) lines from three EBS patients carrying respectively the single heterozygous mutations in KRT5, c.449 T > C, c.980 T > C, and c.608 T > C. All lines display normal karyotype, expressed high levels of pluripotent markers, and can differentiate into derivatives of the three germ layers. These iPSCs are helpful for a better understanding of the EBS pathogenesis and developing novel therapeutic approaches

Generation of two induced pluripotent stem cell lines (UQACi002-A and UQACi005-A) from two patients with KRT14 epidermolysis bullosa simplex mutations

More than 107 pathogenic variations were identified in Keratin 14 gene (KRT14) in patients affected by epidermolysis bullosa simplex (EBS), a rare skin disease with still no curative treatment. Disease models as human induced pluripotent stem cells (hiPSCs) are promising tool for further advance the knowledge about this disorder and accelerate therapies development. Here, two hiPSC lines were reprogrammed from skin fibroblasts of two EBS patients carrying mutations within KRT14 by using CytoTune®Sendai virus. These iPSCs display pluripotent cell morphology, pluripotent markers expression, and the capability to differentiate into the three germ layers

Management of infantile hemangiomas during the COVID pandemic

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided

Reduction in keratin aggregates in epidermolysis bullosa simplex keratinocytes after pretreatment with trimethylamine N-oxide

Epidermolysis bullosa simplex (EBS) is a dominantly inherited skin disease caused by mutations in the keratin 5 (KRT5) or KRT14 genes 1. Some reports suggested that fever and/or hot weather may exacerbate EBS phenotype 2. Effective EBS therapies are still lacking. Molecular chaperones are proteins whose main function is to promote the correct folding of polypeptides (s1). Molecules such as trimethylamine N-oxide (TMAO) and sodium 4-phenylbutyrate (4-PBA) act as chemical chaperones (s2) with protein folding and stabilization activities (s3, s4, s5). Treatment of affected epidermal cells by chemical chaperones to correct the misfolded and aggregated keratins that characterize EBS seems a viable therapeutic option 3. Furthermore, the type I keratins K16 and K17 polymerize with K5, and upregulation of these proteins could replace the mutant K14 in the heterodimer and improve disease pathology (s6). Hence, chemical chaperones which can reduce keratin aggregates formation and upregulate K16 and K17 in EBS-affected cells would be ideal therapeutic candidates for EBS

Gene expression analysis of epidermolysis bullosa simplex with mottled pigmentation

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a subtype of epidermolysis bullosa simplex first reported in 1979. The disease has its onset in early childhood and manifests with either much localized skin blistering, resembling the Weber-Cockayne subtype of EBS, or with more extensive bulla formation as seen in the Koebner subtype of EBS. Associated features include palmoplantar keratoderma and reticular hyperpigmentation unrelated to the blistering

ReproducibiliTea Birmingham

Materials from ReproducibiliTea sessions in Birmingham. Templates and presentations are available for others to use and edit

Severe epidermolysis bullosa simplex phenotype caused by codominant mutations p.Ile377Thr in keratin 14 and p.Gly138Glu in keratin 5

Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French-Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools

Risk Factors for Degree and Type of Sequelae After Involution of Untreated Hemangiomas of Infancy.

IMPORTANCE Infantile hemangiomas involute to some extent, but they often leave sequelae that may cause disfigurement. Factors determining the risk of permanent sequelae after regression are of crucial importance in treatment decision making. OBJECTIVES To describe the sequelae left by infantile hemangiomas after natural involution and to identify clinical characteristics that could predict the most severe or a particular type of sequelae. DESIGN, SETTING, AND PARTICIPANTS Multicentric retrospective cohort study of images from 187 infantile hemangiomas that had not received systemic treatment and had follow-up pictures until regression that were selected from photographic files taken between 2003 and 2013 at 4 university hospitals with large vascular clinics in 3 different countries. MAIN OUTCOMES AND MEASURES Outcome measureswere the type of sequelae classified as residual telangiectasia, anetodermal skin, redundant skin, persistent superficial component, and the degree of sequelae ranging from 1 to 4. RESULTS A total of 184 hemangiomas were included. The overall incidence of significant sequelae was 101 of 184 (54.9%). The most common sequelae after involution were telangiectasias (145, 84.3%), fibrofatty tissue (81, 47.1%), and anetodermic skin (56, 32.6%). The average age at which hemangioma completed involution was 3.5 years. Superficial and deep hemangiomas left significantly fewer sequelae than combined hemangiomas (Mann-Whitney; superficial vs deep, OR, 1.6; 95%CI, 0.6-3.8; P = .81; superficial vs combined, OR, 3.3; 95%CI, 1.7-6.3; P < .001; deep vs combined, OR, 2.1; 95%CI, 0.9-5.1; P < .001). Hemangiomas with a step or abrupt border of the superficial component left more severe sequelae than those with a smooth border (X2,OR, 3.4; 95%CI, 1.8-6.6; P < .001). Superficial hemangiomas with a cobblestone appearance or rough surface left more severe sequelae than those with a smooth surface (Kruskal-Wallis; α, 0.05; P < .001). Using multivariate analysis, combined hemangiomas with a superficial component and a step border were associated with more sequelae. CONCLUSIONS AND RELEVANCE In this retrospective study of sequelae in a large cohort of untreated infants, we quantified the prevalence of permanent scarring and identified clinical features predictive of permanent sequelae. Our observations provide useful information at a time when the treatment paradigm for hemangiomas has changed. Such knowledge may help primary care physicians predict the risk of sequelae and identify high-risk lesions to implement early treatment