Xeroderma Pigmentosum

1. Disease Information

1.1 Disease overview (definition and current understanding)

XP is a multisystemic disorder in which defects in repair of UV-induced DNA lesions (primarily bulky photoproducts) lead to profound photosensitivity with cutaneous and ocular injury, premature skin aging, and multiple early skin malignancies; some genotypes are additionally associated with progressive neurological disease. A practical clinical summary emphasizes: “Strict and consistent sun avoidance and protection and early detection and treatment of premalignant and malignant skin lesions are the mainstays of management,” and that “At present, there is no cure for XP.” (srivastava2021xerodermapigmentosum pages 2-5)

1.2 Key identifiers and controlled vocabulary

• MeSH: Xeroderma Pigmentosum (MeSH ID D014983) as used in ClinicalTrials.gov metadata. (NCT05159752 chunk 1)
• OMIM: XP complementation groups are referenced in the literature excerpt as XP-A to XP-G plus XP-variant (XPV). (schubert2019xerodermapigmentosumand pages 5-6, garciamoreno2023neurologicaldiseasein pages 1-2)
• MONDO / Orphanet / ICD-10 / ICD-11: Not reliably retrievable from the tool-accessible evidence during this run; therefore, MONDO and ORPHA identifiers are not asserted here.

1.3 Synonyms and alternative names

• “Xeroderma pigmentosum”
• “XP”
• “Xeroderma pigmentosum variant” / “XPV” (POLH-associated) (garciamoreno2023neurologicaldiseasein pages 1-2, yurchenko2023genomicmutationlandscape pages 1-2)

1.4 Evidence provenance (patient-level vs aggregated)

The evidence used in this report includes (i) aggregated cohort studies (e.g., UK National XP Service prospective cohort), (ii) tumor genome profiling (multiple tumor genomes from multiple XP groups), (iii) mechanistic in vitro studies in patient-derived cells and engineered models, and (iv) clinical-trial registry data. (garciamoreno2023neurologicaldiseasein pages 1-2, yurchenko2023genomicmutationlandscape pages 1-2, kobaisi2024syntheticrescueof pages 1-2, NCT00002811 chunk 1)

2. Etiology

2.1 Disease causal factors

Primary causal factor: Germline (biallelic) pathogenic variants in DNA repair genes. XP is caused by mutations in NER genes (XPA–XPG; ERCC-family genes; DDB2) or POLH (translesion synthesis). (yurchenko2023genomicmutationlandscape pages 1-2, garciamoreno2023neurologicaldiseasein pages 1-2)

Environmental trigger: UV radiation exposure acts as the dominant environmental driver of DNA damage leading to photosensitivity and carcinogenesis in XP, motivating rigorous photoprotection as the key preventive/therapeutic strategy. (srivastava2021xerodermapigmentosum pages 2-5, NCT03445052 chunk 1)

2.2 Risk factors

• Genetic: Genotype determines mechanism (GG-NER vs TC-NER vs TLS) and influences risk of neurodegeneration and some clinical patterns (see Sections 4 and 6). (garciamoreno2023neurologicaldiseasein pages 1-2, sagun2024differentgermlinevariants pages 1-2)
• Environmental: UV exposure intensity and cumulative exposure are major modifiers of cutaneous carcinogenesis (behavioral adherence is therefore clinically critical). (NCT03445052 chunk 1)

2.3 Protective factors

• Environmental/behavioral: Effective, sustained UV avoidance and photoprotection reduce UVR reaching the face and are the only proven strategy to prevent skin cancer and eye disease in XP; this is the explicit basis for the XPAND behavioral intervention trial. (NCT03445052 chunk 1, srivastava2021xerodermapigmentosum pages 2-5)

2.4 Gene–environment interactions

XP is the archetypal gene–environment interaction disorder: impaired repair of UV-induced lesions causes disproportionate mutagenesis and carcinogenesis under UV exposure, and conversely, strict reduction of UV exposure is expected to reduce mutational input and cancer burden. Tumor-genome data directly demonstrate UV-mutagenesis patterns (e.g., CC>TT signatures) in XP skin cancers. (yurchenko2023genomicmutationlandscape pages 3-5, NCT03445052 chunk 1)

3. Phenotypes

3.1 Core phenotype spectrum (with suggested HPO terms)

Below is a high-yield phenotype list with ontology suggestions (HPO terms are suggested conceptually; exact IDs are not asserted when not tool-verified):

Cutaneous * Severe photosensitivity / exaggerated sunburn reactions (HP: Photosensitivity) * Freckling / lentigines and pigmentary changes (HP: Freckling; HP: Hyperpigmentation; HP: Hypopigmentation) * Telangiectasia, atrophy, xerosis / premature photoaging (HP: Telangiectasia; HP: Cutaneous atrophy; HP: Xerosis) * Multiple early-onset skin cancers: basal cell carcinoma, squamous cell carcinoma, melanoma (HP: Basal cell carcinoma; HP: Squamous cell carcinoma; HP: Melanoma) * Clinical management text describes early detection and treatment of premalignant/malignant lesions as central. (srivastava2021xerodermapigmentosum pages 2-5)

Ophthalmological * Ocular UV sensitivity and damage requiring ophthalmologic surveillance (HP: Photophobia; HP: Keratitis) (not numerically quantified in tool evidence, but included in management follow-up recommendations). (srivastava2021xerodermapigmentosum pages 2-5)

Neurological (subset, genotype-enriched) UK prospective cohort quantified neurological burden and progression: * Neurological symptoms in 36/93 (38.7%) of XP patients. (garciamoreno2023neurologicaldiseasein pages 1-2) * Cerebellar ataxia progression tracked by SARA; significant annual progression in XPD (0.91 points/year, 95% CI 0.61–1.21) and XPA (0.63 points/year, 95% CI 0.38–0.89). (garciamoreno2023neurologicaldiseasein pages 1-2) * Cognitive impairment shows strong genotype dependence (percentages by complementation group): XPA 58.4%, XPC 17.6%, XPD 85.0%, XPE 15.1%, XPG 83.2%, XPV 4.3%. (garciamoreno2023neurologicaldiseasein pages 10-11) * Sensorineural hearing loss in 28/93 (30.1%). (garciamoreno2023neurologicaldiseasein pages 12-13)

Suggested HPO terms: HP: Cerebellar ataxia; HP: Cognitive impairment; HP: Sensorineural hearing impairment; HP: Peripheral neuropathy; HP: Hyporeflexia.

3.2 Age of onset, severity, and progression

• The UK cohort supports that neurological symptoms typically occur after cutaneous/ophthalmologic symptoms and include early- and late-onset forms with genotype clustering in XPA/XPD/XPG. (garciamoreno2023neurologicaldiseasein pages 1-2)
• XP-A genotype–neurodegeneration associations can be stratified into severe/intermediate/mild categories using a scoring approach at age 10 in a US natural-history cohort (n=18). (sagun2024differentgermlinevariants pages 1-2)

3.3 Quality-of-life impacts

XP is highly QoL-limiting due to lifelong UV avoidance, frequent procedures for lesions/cancers, and potential neurologic disability. XPAND explicitly targets adherence barriers to photoprotection because inadequate photoprotection increases cancer burden and life-threatening melanoma risk. (NCT03445052 chunk 1)

4. Genetic / Molecular Information

4.1 Causal genes and complementation groups

XP is defined by biallelic pathogenic variants in eight genotypes (XPA, XPB/ERCC3, XPC, XPD/ERCC2, XPE/DDB2, XPF/ERCC4, XPG/ERCC5, and XPV/POLH). (garciamoreno2023neurologicaldiseasein pages 1-2)

Table: This table summarizes the main xeroderma pigmentosum complementation groups, their causal genes, core repair roles, and whether neurologic involvement is typical or variable. It emphasizes high-yield 2023-2024 evidence plus a practical management overview source useful for clinical interpretation.

4.2 Pathogenic variant classes and functional consequences

• XP results from loss-of-function or hypomorphic variants that reduce NER or TLS capacity; the management-focused mechanism summary describes lesion recognition (XPE/XPC), TFIIH-dependent opening (XPB/XPD), and dual incision by XPG (3′) and XPF/ERCC1 (5′). (srivastava2021xerodermapigmentosum pages 2-5)

Genotype–phenotype (2024 XP-A focus): * A 2024 study of 18 XP-A patients (1973–2023) reports that variant type/location correlates with neurologic severity (severe vs intermediate vs mild) and that reduced repair is greatest in severe disease. (sagun2024differentgermlinevariants pages 1-2)

Founder deep intronic variants (2023 XP-F in Japan): * Senju et al. identified 17 XP-F cases with deep intronic ERCC4/XPF founder variants; an intron 1 founder allele (c.207+196T>A) has MAF ~1/508 and accounts for ~10% of Japanese XP cases; ASOs restored XPF protein and DNA repair activity in cells, motivating precision ASO therapeutics and inclusion of this variant in routine genetic testing for Japanese XP. (senju2023deepintronicfounder pages 5-6, senju2023deepintronicfounder pages 1-2)

4.3 Allele frequencies / population genetics

• Japan has substantially higher XP prevalence than the US/Europe in recent synthesis: ~1 in 22,000 in Japan vs ~1 in 1,000,000 in the US/Europe (reported in 2024 XP-A paper background). (sagun2024differentgermlinevariants pages 1-2)
• Japanese founder ERCC4/XPF intron 1 allele MAF ~0.002 and high contribution to national XP burden. (senju2023deepintronicfounder pages 1-2, senju2023deepintronicfounder pages 5-6)

4.4 Modifier genes (emerging)

A 2024 XP-C experimental study suggests cellular pathways outside canonical NER can modulate XP-C cellular phenotypes: * In XP-C cells, PIK3C3 downregulation increased post-UV survival and promoted ~20% repair of 6-4 photoproducts, with a major UVB resistance shift (LD50 0.056 J/cm² vs 0.013 J/cm² control), implicating autophagy/UVRAG-linked regulation as a phenotype modifier and potential therapeutic target class (preclinical). (kobaisi2024syntheticrescueof pages 2-5, kobaisi2024syntheticrescueof pages 1-2)

4.5 Genetic testing approaches (current practice patterns)

• Diagnosis and trial eligibility often rely on functional DNA repair testing such as unscheduled DNA synthesis (UDS) assays (explicit inclusion criterion in the T4N5 chemoprevention trial) and genetic characterization, with complementation and sequencing used in national services. (NCT00002811 chunk 1, garciamoreno2023neurologicaldiseasein pages 1-2)

5. Epidemiology and Prognosis

5.1 Epidemiology

• Prevalence estimates cited in 2024 XP-A work: ~1/1,000,000 (US/Europe) and ~1/22,000 (Japan). (sagun2024differentgermlinevariants pages 1-2)
• A historical review excerpt reports incidence <1:1,000,000 in the USA/Europe and ~10-fold higher in more isolated populations, with consanguinity ~30% of cases (older data, used here only as context). (schubert2019xerodermapigmentosumand pages 5-6)

5.2 Cancer risk (statistics from recent studies)

Magnitude of risk: * 2023 tumor-genome study summarizes XP as having increased skin cancer risk reaching “several thousand-fold” for some groups, and provides explicit magnitudes: up to 10,000-fold increased risk for non-melanoma skin cancer and 2,000-fold for melanoma; it also notes ~34-fold increased risk of internal tumors (epidemiological evidence). (yurchenko2023genomicmutationlandscape pages 1-2)

Mutation burden as a mechanistic correlate (2023): * XP tumors (GG-NER defects: XP-C/XP-E; TLS defect: XP-V) “harbor 3.6-fold more mutations than sporadic skin cancers, on average.” (yurchenko2023genomicmutationlandscape pages 9-11) * UV-signature CC>TT double-base substitutions are enriched (e.g., XP-C ~0.2 vs sporadic ~0.03 in one comparison), supporting overwhelming UV mutational input when repair is defective. (yurchenko2023genomicmutationlandscape pages 1-2)

5.3 Neurologic prognosis

• Neurological disease is common and progressive in genotype-enriched groups, with measurable annual progression in SARA for XPA and XPD (see Section 3). Mutation severity score can function as a prognostic stratification variable for progression in XPA and XPD and for ADL decline in XPA. (garciamoreno2023neurologicaldiseasein pages 1-2)

6. Diagnostics

6.1 Clinical diagnosis

XP diagnosis is based on clinical features (early photosensitivity, pigmentary change, early skin cancers) plus confirmatory laboratory/genetic evidence. A management-focused description emphasizes multidisciplinary follow-up (pediatrics, dermatology, ophthalmology, neurology). (srivastava2021xerodermapigmentosum pages 2-5)

6.2 Functional laboratory tests

• UDS (unscheduled DNA synthesis) assays are explicitly used as a diagnostic confirmation method (e.g., inclusion for T4N5 trial; and as part of national cohort diagnostic workflows). (NCT00002811 chunk 1, garciamoreno2023neurologicaldiseasein pages 1-2)

6.3 Genetic testing

• Genotype classification across XPA, XPB, XPC, XPD, XPE, XPF, XPG, XPV is core for prognosis (neurological risk), surveillance, and trial stratification; deep intronic founder ERCC4 variants highlight the need to consider non-coding pathogenic alleles in specific populations. (garciamoreno2023neurologicaldiseasein pages 1-2, senju2023deepintronicfounder pages 5-6)

6.4 Differential diagnosis

Not systematically retrievable from tool evidence in this run; however, clinical-trial eligibility explicitly excludes overlap syndromes (Cockayne syndrome, trichothiodystrophy) for some interventions, reflecting key differentials among NER disorders. (NCT00002811 chunk 1)

7. Treatment and Current Applications (real-world implementation)

7.1 Core standard of care (real-world)

• There is no curative therapy; UV avoidance and photoprotection plus early lesion detection/treatment are foundational. (srivastava2021xerodermapigmentosum pages 2-5)
• Recommended care includes “Regular paediatric, dermatological, ophthalmological and neurological follow-up.” (srivastava2021xerodermapigmentosum pages 2-5)

MAXO suggestions (not ID-verified): photoprotection; dermatologic surveillance; excision/ablation of premalignant lesions; topical field therapies; systemic chemoprevention; genetic counseling.

7.2 Chemoprevention and lesion-directed therapies

A clinical summary lists: * Oral isotretinoin (chemoprevention) (srivastava2021xerodermapigmentosum pages 2-5) * Treatment of actinic keratoses and skin cancers by local therapies; topical agents (e.g., imiquimod, fluorouracil) are referenced as part of management options (not quantified here). (srivastava2021xerodermapigmentosum pages 2-5)

7.3 DNA repair enzyme topical therapy (historical but still informative)

T4N5 liposome lotion trial (Phase 3 chemoprevention): * NCT00002811: randomized, double-blind, multicenter trial comparing T4 endonuclease V (T4N5) liposome lotion vs placebo to reduce actinic keratoses and protect against UV skin damage in XP. Enrollment projected 6–30; randomized 2:1 T4N5:placebo; diagnosis confirmed by UDS assay; ages 2–60. (NCT00002811 chunk 1)

7.4 Behavioral intervention to improve photoprotection (implementation science)

XPAND Trial (NCT03445052): * RCT testing a tailored adherence intervention to reduce UVR dose to the face, measured via wrist dosimeter (SEDs) plus 15-minute interval diary weighting for protection behaviors; target sample size 24 (15 actual enrolled). The intervention uses seven sessions and behavior-change techniques and motivational interviewing. (NCT03445052 chunk 2)

7.5 Melanocortin pathway photoprotection strategy (clinical trials; 2023 updates)

Afamelanotide (SCENESSE®) Phase IIa studies: * NCT05159752 (CUV156): open-label Phase IIa in XP-C, evaluating safety and efficacy; primary endpoint change in minimal erythema dose (MED) baseline to day 76; secondary endpoints include UV-induced DNA damage/repair capacity, skin severity measures, melanin density, and QoL tools; afamelanotide implant administered every two weeks for 12 weeks (n=6 planned). Last update posted 2023-06-18; primary completion estimated 2024-03. (NCT05159752 chunk 1) * NCT05370235 (CUV152): open-label Phase IIa in XP-C and XP-V, primary endpoints MED change for each genotype; similar DNA damage/repair and QoL endpoints; recruitment sites include Belgium and Spain; last update posted 2023-09-21; primary completion estimated 2024-06. (NCT05370235 chunk 1)

7.6 Immunotherapy and targeted therapy for XP-associated cancers

A clinical management summary lists immunotherapies and targeted agents used for advanced skin cancers in XP, including pembrolizumab, nivolumab, cemiplimab and vismodegib. (srivastava2021xerodermapigmentosum pages 2-5)

Mechanistic rationale is supported by high tumor mutational burden and UV-mutational signatures in XP skin cancers, which can increase neoantigen load and may contribute to ICI responsiveness (inference supported by tumor-genome findings and the management listing; response rates not quantified here). (yurchenko2023genomicmutationlandscape pages 1-2, srivastava2021xerodermapigmentosum pages 2-5)

8. Prevention

8.1 Primary prevention

Strict UV avoidance and rigorous photoprotection (protective clothing, sunscreen, limiting outdoor exposure) is the cornerstone preventive approach and is explicitly the only means to prevent skin cancer/eye disease in XP clinical management. (NCT03445052 chunk 1)

8.2 Secondary prevention

• Frequent dermatologic surveillance and early treatment of premalignant lesions (actinic keratoses) and skin cancers is a major management theme and the basis for prevention trials (e.g., T4N5). (srivastava2021xerodermapigmentosum pages 2-5, NCT00002811 chunk 1)

8.3 Tertiary prevention

• Disability prevention and symptomatic management for neurologic disease: no effective disease-modifying therapy for neurodegeneration is noted in clinical overview; however, validated scales (SARA, ADL) now quantify progression and can support monitoring and future clinical trials. (srivastava2021xerodermapigmentosum pages 2-5, garciamoreno2023neurologicaldiseasein pages 1-2)

9. Mechanism / Pathophysiology (molecular-to-clinical causal chain)

9.1 Core mechanism: defective NER or TLS

Upstream trigger: UV exposure induces bulky DNA photoproducts.

Molecular defect (NER): Damage recognition by XPE/XPC, assembly/verification via XPA/RPA and TFIIH, DNA unwinding by XPB/XPD, dual incision by XPG and XPF/ERCC1, followed by repair synthesis/ligation. (srivastava2021xerodermapigmentosum pages 2-5)

Variant mechanism (XPV): Defect in POLH compromises error-free bypass of UV lesions during replication, altering mutational spectra. (yurchenko2023genomicmutationlandscape pages 9-11, yurchenko2023genomicmutationlandscape pages 1-2)

Downstream consequences: Failure to remove/bypass UV lesions causes mutations with characteristic UV signatures, high tumor mutation burden, and carcinogenesis; neurologic disease arises in subsets (often those with combined GG-NER/TC-NER disruption). (yurchenko2023genomicmutationlandscape pages 3-5, garciamoreno2023neurologicaldiseasein pages 1-2)

9.2 Tumor genomics as mechanistic readout (2023)

• XP skin cancers show markedly elevated mutational burden and enrichment for UV-associated mutation classes; GG-NER-defective and POLH-defective tumors exhibit distinctive patterns, and overall XP tumors average 3.6-fold more mutations than sporadic skin cancers. (yurchenko2023genomicmutationlandscape pages 9-11)

9.3 Neurological disease mechanisms (current evidence)

The 2023 prospective cohort links genotype to neurologic progression and disability, establishing clinical endpoints (SARA/ADL) and demonstrating mutation-severity association with progression in XPA/XPD. While mechanistic hypotheses (e.g., endogenous lesions such as cyclopurines) are discussed, the key evidence here is phenotypic quantification and genotype stratification. (garciamoreno2023neurologicaldiseasein pages 1-2)

Suggested GO biological-process terms (conceptual): nucleotide excision repair; response to UV; DNA damage recognition; DNA helicase activity; DNA incision, 5′/3′ endonuclease activity; translesion synthesis; regulation of apoptosis.

Suggested CL cell types (conceptual): keratinocyte; melanocyte; fibroblast; peripheral neuron; cochlear neuron.

10. Anatomical structures affected

Primary: skin (UV-exposed areas), eyes; in neurologic XP, brain (cerebellum/global atrophy), peripheral nervous system (neuropathy), auditory system (cochlear involvement). (garciamoreno2023neurologicaldiseasein pages 1-2, garciamoreno2023neurologicaldiseasein pages 12-13)

Suggested UBERON terms (conceptual): skin; epidermis; cornea; retina; cerebellum; peripheral nerve; cochlea.

11. Temporal development

• XP is typically recognized in early life due to photosensitivity and pigmentary change; neurologic disease may present later and progresses measurably in XPA and XPD (annual SARA increases). (garciamoreno2023neurologicaldiseasein pages 1-2)

12. Inheritance and population

• Inheritance: autosomal recessive (explicitly stated in clinical trial description and cohort literature). (NCT03445052 chunk 1)
• Population structure: founder effects can markedly influence national case distributions (e.g., Japanese ERCC4/XPF deep intronic founder allele). (senju2023deepintronicfounder pages 5-6)

13. Other species / natural disease and 14. Model organisms

Model organism and cross-species natural disease information were not retrievable from the tool-accessible evidence in this run; therefore, no curated statements are made here.

15. Recent developments and latest research highlights (2023–2024)

1) Neurologic natural history and endpoints (Brain, Dec 2023): 93-patient prospective cohort; neurological symptoms in 38.7%; genotype-specific frequencies; quantified progression in XPA and XPD; proposes mutation severity as a prognostic biomarker for trial stratification. Publication date: Dec 2023. URL: https://doi.org/10.1093/brain/awad266 (garciamoreno2023neurologicaldiseasein pages 1-2)

2) XP-A genotype–neurodegeneration correlation (PLOS Genetics, Dec 2024): 18 XP-A patients examined across 1973–2023; XPA variant type/location associated with severe/intermediate/mild neurodegeneration; reinforces >1000-fold skin-cancer risk framing and provides contemporary prevalence estimates. Publication date: Dec 2024. URL: https://doi.org/10.1371/journal.pgen.1011265 (sagun2024differentgermlinevariants pages 1-2)

3) Tumor genome landscape (Nature Communications, May 2023): 38 XP skin-cancer genomes; high mutation burdens, UV signatures, and group-specific mutation patterns; provides quantitative risk magnitudes (up to 10,000-fold non-melanoma, 2,000-fold melanoma) and internal tumor risk framing. Publication date: May 2023. URL: https://doi.org/10.1038/s41467-023-38311-0 (yurchenko2023genomicmutationlandscape pages 1-2)

4) Precision therapeutics for founder deep intronic variants (PNAS, Jun 2023): ERCC4/XPF deep intronic founder alleles in Japan; ASO correction restores repair in patient cells; recommends including founder intron variant in testing. Publication date: Jun 2023. URL: https://doi.org/10.1073/pnas.2217423120 (senju2023deepintronicfounder pages 5-6)

5) Synthetic rescue strategy in XP-C (Cell Death & Disease, Nov 2024): kinase siRNA screen identifies PIK3C3; knockdown yields ~20% 6-4PP repair and improves UVB resistance (LD50 shift); supports autophagy/UVRAG-linked modulation as a potential therapeutic direction. Publication date: Nov 2024. URL: https://doi.org/10.1038/s41419-024-07186-4 (kobaisi2024syntheticrescueof pages 2-5)

Notes on evidence limitations

• PMIDs: The tool-accessible excerpts provided DOIs and journal metadata but did not reliably surface PMIDs for the key 2023–2024 sources; therefore, PMIDs are not asserted.
• MONDO/Orphanet/ICD identifiers: Not available from tool evidence in this run.
• Model organism evidence: Not available from tool evidence in this run.

Key data points (quick reference)

• Neurologic symptoms: 38.7% (36/93) in UK cohort; SARA progression 0.91 points/year (XPD) and 0.63 points/year (XPA). (garciamoreno2023neurologicaldiseasein pages 1-2)
• Cognitive impairment frequencies: XPD 85.0%, XPG 83.2%, XPA 58.4%, XPC 17.6%, XPV 4.3%. (garciamoreno2023neurologicaldiseasein pages 10-11)
• Skin cancer risk magnitude: up to 10,000-fold (non-melanoma) and 2,000-fold (melanoma) increases reported in 2023 tumor-genome study background. (yurchenko2023genomicmutationlandscape pages 1-2)
• Tumor mutational burden: XP tumors average 3.6-fold more mutations than sporadic skin cancers. (yurchenko2023genomicmutationlandscape pages 9-11)
• Founder ERCC4 intron 1 allele: MAF ~1/508, accounting for ~10% of Japanese XP; ASOs restore repair in cells. (senju2023deepintronicfounder pages 5-6)
• Clinical trials: T4N5 topical DNA repair enzyme lotion (NCT00002811) (NCT00002811 chunk 1); afamelanotide Phase IIa studies (NCT05159752, NCT05370235) with MED and DNA damage endpoints (NCT05159752 chunk 1, NCT05370235 chunk 1); photoprotection adherence RCT XPAND (NCT03445052) using dosimetry (NCT03445052 chunk 2).

References

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5. (kobaisi2024syntheticrescueof pages 1-2): Farah Kobaisi, Eric Sulpice, Ali Nasrallah, Patricia Obeïd, Hussein Fayyad-Kazan, Walid Rachidi, and Xavier Gidrol. Synthetic rescue of xeroderma pigmentosum c phenotype via pik3c3 downregulation. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07186-4, doi:10.1038/s41419-024-07186-4. This article has 2 citations and is from a peer-reviewed journal.

6. (srivastava2021xerodermapigmentosum pages 2-5): Gautam Srivastava and G. Srivastava. Xeroderma pigmentosum. Oxford Medical Case Reports, Jan 2021. URL: https://doi.org/10.1093/omcr/omab107, doi:10.1093/omcr/omab107. This article has 3 citations and is from a peer-reviewed journal.

7. (NCT05159752 chunk 1): A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum (XP). Clinuvel Europe Limited. 2021. ClinicalTrials.gov Identifier: NCT05159752

8. (schubert2019xerodermapigmentosumand pages 5-6): Steffen Schubert and Steffen Emmert. Xeroderma pigmentosum and related diseases. ArXiv, pages 1743-1768, Dec 2019. URL: https://doi.org/10.1002/9781119142812.ch138, doi:10.1002/9781119142812.ch138. This article has 3 citations.

9. (NCT00002811 chunk 1): T4N5 Liposome Lotion Compared With Placebo Lotion for Preventing Actinic Keratoses in Patients With Xeroderma Pigmentosum. Applied Genetics. 1996. ClinicalTrials.gov Identifier: NCT00002811

10. (NCT03445052 chunk 1): XPAND Trial: Enhancing XP Photoprotection Activities - New Directions. Guy's and St Thomas' NHS Foundation Trust. 2018. ClinicalTrials.gov Identifier: NCT03445052

11. (yurchenko2023genomicmutationlandscape pages 3-5): Andrey A. Yurchenko, Fatemeh Rajabi, Tirzah Braz-Petta, Hiva Fassihi, Alan Lehmann, Chikako Nishigori, Jinxin Wang, Ismael Padioleau, Konstantin Gunbin, Leonardo Panunzi, Fanny Morice-Picard, Pierre Laplante, Caroline Robert, Patricia L. Kannouche, Carlos F. M. Menck, Alain Sarasin, and Sergey I. Nikolaev. Genomic mutation landscape of skin cancers from dna repair-deficient xeroderma pigmentosum patients. Nature Communications, May 2023. URL: https://doi.org/10.1038/s41467-023-38311-0, doi:10.1038/s41467-023-38311-0. This article has 49 citations and is from a highest quality peer-reviewed journal.

12. (garciamoreno2023neurologicaldiseasein pages 10-11): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

13. (garciamoreno2023neurologicaldiseasein pages 12-13): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

14. (garciamoreno2023neurologicaldiseasein pages 3-4): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

15. (garciamoreno2023neurologicaldiseasein pages 2-3): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

16. (garciamoreno2023neurologicaldiseasein pages 11-12): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

17. (garciamoreno2023neurologicaldiseasein pages 9-10): Hector Garcia-Moreno, Douglas R Langbehn, Adesoji Abiona, Isabel Garrood, Zofia Fleszar, Marta Antonia Manes, Ana M Susana Morley, Emma Craythorne, Shehla Mohammed, Tanya Henshaw, Sally Turner, Harsha Naik, Istvan Bodi, Robert P E Sarkany, Hiva Fassihi, Alan R Lehmann, and Paola Giunti. Neurological disease in xeroderma pigmentosum: prospective cohort study of its features and progression. Brain, 146:5044-5059, Dec 2023. URL: https://doi.org/10.1093/brain/awad266, doi:10.1093/brain/awad266. This article has 20 citations and is from a highest quality peer-reviewed journal.

18. (senju2023deepintronicfounder pages 5-6): Chikako Senju, Yuka Nakazawa, Taichi Oso, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, and Tomoo Ogi. Deep intronic founder mutations identified in the ercc4/xpf gene are potential therapeutic targets for a high-frequency form of xeroderma pigmentosum. Proceedings of the National Academy of Sciences of the United States of America, Jun 2023. URL: https://doi.org/10.1073/pnas.2217423120, doi:10.1073/pnas.2217423120. This article has 14 citations and is from a highest quality peer-reviewed journal.

19. (senju2023deepintronicfounder pages 2-3): Chikako Senju, Yuka Nakazawa, Taichi Oso, Mayuko Shimada, Kana Kato, Michiko Matsuse, Mariko Tsujimoto, Taro Masaki, Yasushi Miyazaki, Satoshi Fukushima, Satoshi Tateishi, Atsushi Utani, Hiroyuki Murota, Katsumi Tanaka, Norisato Mitsutake, Shinichi Moriwaki, Chikako Nishigori, and Tomoo Ogi. Deep intronic founder mutations identified in the ercc4/xpf gene are potential therapeutic targets for a high-frequency form of xeroderma pigmentosum. Proceedings of the National Academy of Sciences of the United States of America, Jun 2023. URL: https://doi.org/10.1073/pnas.2217423120, doi:10.1073/pnas.2217423120. This article has 14 citations and is from a highest quality peer-reviewed journal.

20. (yurchenko2023genomicmutationlandscape pages 9-11): Andrey A. Yurchenko, Fatemeh Rajabi, Tirzah Braz-Petta, Hiva Fassihi, Alan Lehmann, Chikako Nishigori, Jinxin Wang, Ismael Padioleau, Konstantin Gunbin, Leonardo Panunzi, Fanny Morice-Picard, Pierre Laplante, Caroline Robert, Patricia L. Kannouche, Carlos F. M. Menck, Alain Sarasin, and Sergey I. Nikolaev. Genomic mutation landscape of skin cancers from dna repair-deficient xeroderma pigmentosum patients. Nature Communications, May 2023. URL: https://doi.org/10.1038/s41467-023-38311-0, doi:10.1038/s41467-023-38311-0. This article has 49 citations and is from a highest quality peer-reviewed journal.

21. (kobaisi2024syntheticrescueof pages 2-5): Farah Kobaisi, Eric Sulpice, Ali Nasrallah, Patricia Obeïd, Hussein Fayyad-Kazan, Walid Rachidi, and Xavier Gidrol. Synthetic rescue of xeroderma pigmentosum c phenotype via pik3c3 downregulation. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07186-4, doi:10.1038/s41419-024-07186-4. This article has 2 citations and is from a peer-reviewed journal.

22. (NCT03445052 chunk 2): XPAND Trial: Enhancing XP Photoprotection Activities - New Directions. Guy's and St Thomas' NHS Foundation Trust. 2018. ClinicalTrials.gov Identifier: NCT03445052

23. (NCT05370235 chunk 1): A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum C and V. Clinuvel Europe Limited. 2022. ClinicalTrials.gov Identifier: NCT05370235

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