Xeroderma Pigmentosum Research Articles

Sequential post-translational modifications regulate damaged DNA-binding protein DDB2 function.

Nucleotide excision repair (NER) is a major DNA repair system and hereditary defects in this system cause critical genetic diseases (e.g. xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy). Various proteins are involved in the eukaryotic NER system and undergo several post-translational modifications. Damaged DNA-binding protein 2 (DDB2) is a DNA damage recognition factor in the NER pathway. We previously demonstrated that DDB2 was SUMOylated in response to UV irradiation; however, its physiological roles remain unclear. We herein analysed several mutants and showed that the N-terminal tail of DDB2 was the target for SUMOylation; however, this region did not contain a consensus SUMOylation sequence. We found a SUMO-interacting motif (SIM) in the N-terminal tail that facilitated SUMOylation. The ubiquitination of a SUMOylation-deficient DDB2 SIM mutant was decreased, and its retention of chromatin was prolonged. The SIM mutant showed impaired NER, possibly due to a decline in the timely handover of the lesion site to XP complementation group C. These results suggest that the SUMOylation of DDB2 facilitates NER through enhancements in ubiquitination.

Skin Cancer Induction by the Antimycotic Drug Voriconazole Is Caused by Impaired DNA Damage Detection Due to Chromatin Compaction

Phototoxicity and skin cancer are severe adverse effects of the anti-fungal drug Voriconazole (VOR). These adverse effects resemble those seen in xeroderma pigmentosum (XP), caused by defective DNA nucleotide excision repair (NER), and we show that VOR decreases NER capacity. We show that VOR treatment does not perturb the expression of NER, or other DNA damage-related genes, but that VOR localizes to heterochromatin, in complexes containing histone acetyltransferase GCN5. Impairment of GCN5 binding to histone H3 reduced acetylation of H3, restricting damage-dependent chromatin unfolding, thereby reducing NER initiation. Restoration of H3 histone acetylation using histone deacetylase inhibitors (HDACi), rescued VOR-induced NER repression, thus offering a preventive therapeutic option. These findings underline the importance of DNA damage-dependent chromatin remodeling as an important prerequisite of functional DNA repair.

Genome-wide analysis of transcription-coupled repair reveals novel transcription events in Caenorhabditis elegans.

Bulky DNA adducts such as those induced by ultraviolet light are removed from the genomes of multicellular organisms by nucleotide excision repair, which occurs through two distinct mechanisms, global repair, requiring the DNA damage recognition-factor XPC (xeroderma pigmentosum complementation group C), and transcription-coupled repair (TCR), which does not. TCR is initiated when elongating RNA polymerase II encounters DNA damage, and thus analysis of genome-wide excision repair in XPC-mutants only repairing by TCR provides a unique opportunity to map transcription events missed by methods dependent on capturing RNA transcription products and thus limited by their stability and/or modifications (5'-capping or 3'-polyadenylation). Here, we have performed eXcision Repair-sequencing (XR-seq) in the model organism Caenorhabditis elegans to generate genome-wide repair maps in a wild-type strain with normal excision repair, a strain lacking TCR (csb-1), and a strain that only repairs by TCR (xpc-1). Analysis of the intersections between the xpc-1 XR-seq repair maps with RNA-mapping datasets (RNA-seq, long- and short-capped RNA-seq) reveal previously unrecognized sites of transcription and further enhance our understanding of the genome of this important model organism.

Protein-protein interactions in the core nucleotide excision repair pathway

Nucleotide excision repair (NER) clears genomes of DNA adducts formed by UV light, environmental agents, and antitumor drugs. Gene mutations that lead to defects in the core NER reaction cause the skin cancer-prone disease xeroderma pigmentosum. In NER, DNA lesions are excised within an oligonucleotide of 25–30 residues via a complex, multi-step reaction that is regulated by protein-protein interactions. These interactions were first characterized in the 1990s using pull-down, co-IP and yeast two-hybrid assays. More recently, high-resolution structures and detailed functional studies have started to yield detailed pictures of the progression along the NER reaction coordinate. In this review, we highlight how the study of interactions among proteins by structural and/or functional studies have provided insights into the mechanisms by which the NER machinery recognizes and excises DNA lesions. Furthermore, we identify reported, but poorly characterized or unsubstantiated interactions in need of further validation.

Revealing the UV response of melanocytes in xeroderma pigmentosum group A using patient-derived induced pluripotent stem cells

BackgroundXeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes: MCs) as disease target cells, establishing MCs in primary cultures is challenging. ObjectiveElucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation. MethodsiPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12 h after irradiation with 30 or 150 J/m2 of UV-B using microarray analysis. ResultsXP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150 J/m2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30 J/m2 UV exposure. ConclusionWe revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.

The association between XPD rs13181 and rs1799793 polymorphism and oral cancer risk: evidence from a meta-analysis

ObjectiveSingle nucleotide polymorphisms (SNPs) are common in genes and can lead to dysregulation of gene expression in tissues, which can affect carcinogenesis. Many studies reporting the association between xeroderma pigmentosum group D (XPD) polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results.MethodsWe performed a comprehensive and systematic search through the PubMed, Elsevier, Web of science, and Embase databases, twelve studies were included in the meta-analysis to determine whether XPD rs13181 and rs1799793 polymorphism contributed to the risk of oral cancer.ResultsThe pooled date indicated a significant association between the rs13181 polymorphism and oral cancer risk for the allele comparison model (odds ratio, OR = 1.60, 95% confidence intervals, CI = 1.09–2.35, P = 0.02), the dominant model (OR = 1.74, 95% CI = 1.08–2.82, P = 0.02), and the heterozygote model (OR = 1.59, 95% CI = 1.02–2.49, P = 0.04). For the XPD rs1799793 polymorphism, it is not associated with the incidence of oral cancer under any model. Subgroup analyses based on ethnicity indicated that the rs13181 polymorphism increased the risk of oral cancer among Asians according to the allele comparison model (OR = 1.97, 95% CI = 1.10–3.51, P = 0.02), the dominant model (OR = 2.35, 95% CI = 1.25–4.44, P = 0.008), the heterozygote model (OR = 2.05, 95% CI = 1.15–3.66, P = 0.01), and the homozygous model (OR = 2.47, 95% CI = 1.06–5.76, P = 0.04).ConclusionOur meta-analysis suggests a positive correlation between XPD rs13181polymorphism and the development of oral cancer among Asians, but a negative correlation among Caucasians populations.

The Expression of PRAME as an Aid for Diagnosis and Evaluation of Histologic Margins of Intraepidermal Cutaneous Melanoma in Xeroderma Pigmentosum Patients.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases.

Development and evaluation of a personalised psychological intervention to improve adherence to photoprotection in adults with Xeroderma Pigmentosum (XP)

Development and evaluation of a personalised psychological intervention to improve adherence to photoprotection in adults with Xeroderma Pigmentosum (XP)

Dermoscopy and In Vivo Confocal Microscopy Findings of Basal Cell Carcinomas in Xeroderma Pigmentosum Patients.

Xeroderma pigmentosum (XP) is a rare inherited disorder with a high incidence of malignant tumours. Literature data on dermoscopic and in vivo reflectance confocal microscopy (RCM) findings in patients with XP are very limited. Dermoscopic findings in 32 biopsy-proven BCCs and RCM findings in 10 biopsy-proven BCCs developed in seven XP patients were reviewed. Of 32 BCCs, 28 were pigmented. On dermoscopy, BCCs exhibited multiple grey-blue globules/dots (81, 3%), short-fine telangiectasias/fine arborising vessels (65, 6%), multiple grey-blue ovoid nests (53, 1%), white structures (white-red structureless areas/shiny white areas/lines/strands) (56, 3%), arborising vessels (37, 5%), brown nests/globules/dots (28, 1%), spoke-wheel structures (9, 4%), leaf-like areas (9, 4%), ulceration (28, 1%), peripheral network (21, 9%), and multiple aggregated yellow-white globules (3, 1%). In 10 lesions in which further imaging with RCM was performed, RCM findings differentiated BCC from other tumours, including primary melanoma. Although the dominancy of pigmented structures may imitate melanoma clinically, dermoscopy is a valuable tool in the early diagnosis of BCCs in patients with XP. For suspicious lesions, RCM can help in differentiating pigmented BCC from primary melanoma.

A rare occurrence of Hodgkin lymphoma in a Xeroderma pigmentosum patient: A case report and literature review

Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation, resulting in an increased risk of skin cancer and other UV-induced malignancies. Reports of hematological malignancies occurring in patients with XP are found in the literature, but they seem to be quite rare. This report describes a 29-year-old male patient with XP who developed Hodgkin lymphoma. The potential increased risk of lymphoma in XP patients is highlighted in this paper; however, further studies are needed to better understand the underlying mechanisms of lymphomagenesis in XP patients and to develop optimal treatment strategies for hematological and other internal malignancies in this setting.

Sun Safety Struggles Among Children with Xeroderma Pigmentosum in a Tropical Low-Income Country

Sun Safety Struggles Among Children with Xeroderma Pigmentosum in a Tropical Low-Income Country

Evidence for persistent UV-induced DNA damage and altered DNA damage response in xeroderma pigmentosa patient corneas

Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by injury to the ocular surface due to exposure to ultraviolet (UV) radiation. UV-induced damage in the cells leads to the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidone photoproducts that are repaired by the NER (Nucleotide Excision Repair) pathway. Mutations in the genes coding for NER proteins, as reported in XP patients, would lead to sub-optimal damage repair resulting in clinical signs varying from photo-keratitis to cancerous lesions on the ocular surface. Here, we aimed to provide evidence for the accumulation of DNA damage and activation of DNA repair pathway proteins in the corneal cells of patients with XP. Corneal buttons of patients who underwent penetrating keratoplasty were stained to quantify DNA damage and the presence of activated DNA damage response proteins (DDR) using specific antibodies. Positive staining for pH2A.X and thymidine dimers confirmed the presence of DNA damage in the corneal cells. Positive cells were found in both control corneas and XP samples however, unlike normal tissues, positive cells were found in all cell layers of XP samples indicating that these cells were sensitive to very low levels of UV. pH2A.X-positive cells were significantly more in XP corneas (p < 0.05) indicating the presence of double strand breaks in these tissues. A positive expression of phosphorylated-forms of DDR proteins was noted in XP corneas (unlike controls) such as ataxia telangiectasia mutated/Rad-3 related proteins (ATM/ATR), breast cancer-1 and checkpoint kinases-1 and -2. Nuclear localization of XPA was noted in XP samples which co-localized (calculated using Pearson's correlation) with pATM (0.9 ± 0.007) and pATR (0.6 ± 0.053). The increased presence of these in the nucleus confirms that unresolved DNA damage was accumulating in these cells thereby leading to prolonged activation of the damage response proteins. An increase in pp53 and TUNEL positive cells in the XP corneas indicated cell death likely driven by the p53 pathway. For comparison, cultured normal corneal epithelial cells were exposed to UV-radiation and stained for DDR proteins at 3, 6 and 24 h after irradiation to quantify the time taken by cells with intact DDR pathway to repair damage. These cells, when exposed to UV showed nuclear translocation of DDR proteins at 3 and 6 h which reduced significantly by 24 h confirming that the damaged DNA was being actively repaired leading to cell survival. The persistent presence of the DDR proteins in XP corneas indicates that damage is being actively recognized and DNA replication is stalled, thereby causing accumulation of damaged DNA leading to cell death, which would explain the cancer incidence and cell loss reported in these patients.

XPC Protects against Carcinogen-Induced Histologic Progression to Lung Squamous Cell Carcinoma by Reduced Basal Epithelial Cell Proliferation.

Lung squamous cell carcinoma (LUSC) is the second leading cause of lung cancer. Although characterized by high DNA mutational burdens and genomic complexity, the role of DNA repair in LUSC development is poorly understood. We sought to better understand the role of the DNA repair protein Xeroderma Pigmentosum Group C (XPC) in LUSC development. XPC knock-out (KO), heterozygous, and wild-type (WT) mice were exposed topically to N-nitroso-tris-chloroethylurea (NTCU), and lungs were evaluated for histology and pre-malignant progression in a blinded fashion at various time-points from 8-24 weeks. High-grade dysplasia and LUSC were increased in XPC KO compared with XPC WT NTCU mice (56% vs. 34%), associated with a higher mean LUSC lung involvement (p < 0.05). N-acetylcysteine pre-treatment decreased bronchoalveolar inflammation but did not prevent LUSC development. Proliferation, measured as %Ki67+ cells, increased with NTCU treatment, in high-grade dysplasia and LUSC, and in XPC deficiency (p < 0.01, ANOVA). Finally, pre-LUSC dysplasia developed earlier and progressed to higher histologic classification sooner in XPC KO compared with WT mice. Overall, this supports the protective role of XPC in squamous dysplasia progression to LUSC. Mouse models of early LUSC development are limited; this may provide a valuable model to study mechanisms of LUSC development and progression.

Clinical prognostic significance of xeroderma pigmentosum group C and IFN‑γ in non‑small cell lung cancer.

Lung cancer is the most common cancer in the world due to its high incidence and recurrence. Genetic instability is one of the main factors leading to its occurrence, development and poor prognosis. Decreased xeroderma pigmentosum group C (XPC) expression notably enhances the stem cell properties of lung cancer cells and increases their proliferation and migration. Additionally, patients with lung cancer and low XPC expression had a poor prognosis. The purpose of the present study was to analyze the effect of XPC and IFN-γ on the clinical prognosis of patients with non-small cell lung cancer (NSCLC). Lung adenocarcinoma specimens were collected from a total of 140 patients with NSCLC. Additionally, from these 140 patients, 48 paracarcinoma tissue specimens were also collected, which were later used to construct tissue microarrays. The expression of XPC and IFN-γ in cancer tissues and in paraneoplastic tissues was detected using immunohistochemistry. The prognosis and overall survival of patients were determined through telephone follow-up. The results showed a positive correlation between expression of XPC and IFN-γ in NSCLC. Additionally, high expression of both markers was associated with a favorable prognosis in patients with NSCLC. The aforementioned findings suggest that the expression of XPC and IFN-γ has prognostic value in clinical practice and is expected to become a marker for clinical application.

Human and animal cells under influence of different lighting and stimulus

Circadian rhythms, are the basis of homeostasis of organisms like human and other mammals. Violation of circadian rhythms leads to the development of pathological conditions and severe course of preexisting pathologies. For example some work with B16-F1O cells (B16) has shown that molecules like opsins, Circadian Locomotor Output Cycles Kaput (CLOCK) and clock genes are changed after a white light pulse (WLP). Like this, melanopsin (OPN4) and rhodopsin (OPN2) through UVA irradiation induced B16 pigmentation. Thus, heat shock reduces secreted rhodopsin expression in normal Melan-a melanocytes, while the opposite effect is found in malignant B16 cells. In both cell lines UVA radiation increases the expression of melanopsin and melanin, interfering with several clock genes, and also increasing the DNA repair enzyme xeroderma pigmentosum, complementation group A (XPA). Furthermore, B16 are more responsive to UVA radiation when compared to normal cells. Thereby, opsins are involved in animal camouflage. And their functions in humans involve different wavelengths, for example in skin the keratinocyte differentiation by (410 nm) involved cone opsin (OPN1) and rhodopsin (OPN2), like this in epidermal keratinocytes irradiation by (447 nm) accelerates closure in wound-healing and violet light (415 nm) induced hyperpigmentation. Furthermore, in B16 cell culture certain wavelengths induce proliferation or inhibition like signs of apoptosis and necrosis. Finally understanding the response of opsins and clock genes to different wavelengths in the skin, we could attribute a therapeutic of photobiomodulation (PBM) to approach various dermatological conditions, such as psoriasis, atopic dermatitis, hair growth, wound healing and tissue regeneration.

Abstract 5050: Germline variants in CDKN2A wild-type melanoma prone families

Abstract The presence of germline pathogenic variants in CDKN2A is a well-established underlying cause of familial malignant melanoma. While pathogenic variants in several other genes have also been linked to melanoma development, many familial cases remain unexplained. We analyzed for pathogenic germline variants in a panel of 360 cancer related genes in a set of 56 Norwegian melanoma prone families. The index cases and families were selected based on familial history of melanoma and/or multiple primary melanomas in the same individual, along with previous negative tests for pathogenic CDKN2A variants. We found 6 out of 56 index individuals to carry germline pathogenic or likely pathogenic variants. These variants were found in BRCA2, MRE11, ATM, MSH2, CHEK2 and AR. In addition, one family member with a melanoma diagnosis (not index case) carried a pathogenic variant in MAP3K6. In genes typically linked to xeroderma pigmentosum, we found a high fraction of variants previously considered benign and/or as variants of uncertain significance. In particular the XPCL48F variant was found in 8 out of 56 indexes, thus, the allele fraction (0.07) was significantly higher than in comparable healthy populations (p-values from 0.007 to 0.014). Similarly, we found presumed benign or uncertain variants in MC1R to be significantly enriched or numerically higher in index cases versus comparable healthy populations (p-values from 0.009 to 0.1). The common MC1RArg151Cys variant was highly enriched in our cohort (p=0.001).In conclusion, we found that several melanoma prone families harbored pathogenic variants in genes not usually linked to melanoma. Citation Format: Stian Knappskog, Gjertrud T. Iversen, Marie Loeng, Amalie L. Holth, Per E. Lonning, Jurgen Geisler. Germline variants in CDKN2A wild-type melanoma prone families [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5050.

Relationship between XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 Polymorphisms and the Susceptibility to Head and Neck Carcinoma: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

Background and Objectives: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. Materials and Methods: PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Results: Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of rs17655 polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; p-value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; p-value is 0.008) of the rs751402 polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; p-value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; p-value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; p-value is 0.04) genotypes were associated with an increased risk of HNC. Conclusions: The analysis identified two polymorphisms, rs17655 and rs751402, as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations.

Interpretation on genetic tumour syndromes in the 5th WHO classification of paediatric tumours: part Ⅱ

WHO firstly published the classification of paediatric tumours, in which genetic tumour syndromes were introduced as a separate chapter, covering the clinicopathological features, molecular genetic alterations, and diagnostic criteria of various tumor susceptibility syndromes common in children. This article briefly introduces and interprets 5 hotspot genetic tumour syndromes (neurofibromatosis type 1, naevoid basal cell carcinoma syndrome, von Hippel-Lindau syndrome, familial adenomatous polyposis and xeroderma pigmentosum) based on relevant literature, in order to bring new perspectives and insights to pathologists and clinicians.

Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair

Nucleotide excision repair (NER) promotes genomic integrity by removing bulky DNA adducts introduced by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the ss/ds DNA junction. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido-L-phenylalanine (4AZP or pAzF) was incorporated at Arg-158 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent XPA protein (XPACy3) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA. Here we describe methods to generate XPACy3 and detail in vitro experimental conditions required to stably maintain the protein during biochemical and biophysical studies.

Translating patient needs into medical device development: co-design of a photoprotection visor for Xeroderma Pigmentosum using qualitative interviews

IntroductionPeople with Xeroderma Pigmentosum (XP) have a heightened sensitivity to ultraviolet radiation (UVR) and are advised to wear photoprotective clothing including a visor covering the face and neck. Photoprotective visors are homemade and predominately worn by children with decreasing frequency as age increases. To improve upon the current design and efficacy we were tasked with developing a prototype visor to meet patients’ needs.MethodsAdopting a codesign methodology, patients’ experiences of wearing a visor and patient and carer views of emerging prototypes were explored during interviews. A thematic analysis was conducted in parallel with data collection and themes were interpreted into design cues; desirable attributes of a visor that would counteract the negative user experiences and meet the requirements described by patients and carers. The design cues guided the iterative development of prototypes by academic engineers.ResultsTwenty-four interviews were conducted with patients and carers. Thematic analysis resulted in the following five themes: Being safe from UVR exposure; self-consciousness; temperature effects; acoustic difficulties; and material properties. The following design cues were developed from the themes respectively; materials and design with high UVR protection; ability to customise with own headwear; ventilation to reduce steaming up; acoustic functionality to enable hearing and speech; foldable, portable, and easy to put on and take off.ConclusionsIt is important to understand people’s experiences of using medical devices to improve their safety, efficiency and user satisfaction. The user experience themes and design cues, informed the iterative development of low fidelity visor prototypes as part of a codesign process. These design cues and responses to the prototypes are guiding commercial manufacturing and regulatory approval. The visor can then be prescribed to patients, providing an equitable service of care.