SNP Array Screening and Long Range PCR-Based Targeted Next Generation Sequencing for Autosomal Recessive Disease with Consanguinity: Insight from a Case of Xeroderma Pigmentosum Group C.

Advances in genetic technologies have made genetic testing more accessible than ever before. However, depending on national, regional, legal, and health insurance circumstances, testing procedures may still need to be streamlined in real-world clinical practice. In cases of autosomal recessive disease with consanguinity, the mutation locus is necessarily isodisomy because both alleles originate from a common ancestral chromosome. Based on this premise, we implemented integrated genetic diagnostic methods using SNP array screening and long range PCR-based targeted NGS in a Japanese patient with xeroderma pigmentosum (XP) under the limitation of the national health insurance system. SNP array results showed isodisomy only in XPC and ERCC4 loci. NGS, with a minimal set of long-range PCR primers, detected a homozygous frameshift mutation in XPC; NM_004628.5:c.218_219insT p.(Lys73AsnfsTer9), confirmed by Sanger sequencing, leading to a rapid diagnosis of XP group C. This shortcut strategy is applicable to all autosomal recessive diseases caused by consanguineous marriages, especially in scenarios with a moderate number of genes to test, a common occurrence in clinical genetic practice.

Brazilian XP-E siblings carrying a novel DDB2 variant developed early-onset melanoma: a case report.

BACKGROUND: Xeroderma pigmentosum group E (XP-E) is one of the least common forms of XP, a rare syndrome where patients are prone to develop skin cancer in exposed sunlight areas. XP-E patients are generally not diagnosed until they are adults due to the mild phenotype. CASE PRESENTATION: two XP-E siblings, female, 23 years, and male, 25 years, from a Brazilian consanguineous family carrying the novel missense pathogenic variant in DDB2 gene, NM_000107.3:c.1027G > C, associated with skin cancer early-onset and severe phenotype, as nodular melanoma in the cornea and in the ear. CONCLUSION: The assessment of genomic variant pathogenicity was a challenge since this family belongs to an underrepresented population in genomic databases. Given the scarcity of literature documenting XP-E cases and the challenges encountered in achieving an early diagnosis, this report emphasizes the imperative of sun protection measures in XP-E patients. Additionally, it highlights the detrimental impact of the COVID-19 pandemic on cancer diagnosis, leading to the manifestation of a severe phenotype in affected individuals.

Identifying the psychosocial predictors of ultraviolet exposure to the face in patients with xeroderma pigmentosum: a study of the behavioural factors affecting clinical outcomes in this genetic disease.

BACKGROUND: For patients with xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR), particularly for the face. We have recently developed a methodology for objectively measuring photoprotection behaviour ('UVR dose to facial skin') and have found that the degree of photoprotection varies greatly between patients with XP. We have previously identified factors affecting photoprotection behaviour in XP using a subjective measure of photoprotection. Here, we have used this objective methodology to identify the factors which determine photoprotection behaviour in XP. METHODS: We studied 29 psychological, social, demographic and clinical variables in 36 patients with XP. We have previously objectively measured UVR protection (by measuring the dose of UVR reaching the skin of the face over a 3-week period) in these patients. Here, we use linear mixed-effects model analysis to identify the factors which lead to the differences in degree of photoprotection observed in these patients. RESULTS: Psychosocial factors accounted for as much of the interindividual variation in photoprotection behaviour (29%) as demographic and clinical factors (24%). Psychosocial factors significantly associated with worse UVR protection included: automaticity of the behaviours, and a group of beliefs and perceptions about XP and photoprotection known to associate with poor treatment adherence in other diseases. CONCLUSIONS: We have identified factors contributing to poor photoprotection in XP. Identifying these potentially reversible psychosocial features has enabled us to design an intervention to improve photoprotection in patients with XP, aiming to prevent skin and eye cancers in these patients.

Increased risk of internal tumors in DNA repair-deficient xeroderma pigmentosum patients: analysis of four international cohorts.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare, autosomal, recessive DNA repair-deficiency disorder with a frequency of 1-3 per million livebirths in Europe and USA but with higher frequencies in isolated islands or in countries with a high level of consanguinity. XP is characterized by high incidence of skin cancers on sun-exposed sites. Recent improvement in life expectancy of XP patients suggests an increased risk of frequently aggressive and lethal internal tumors. Our purpose was to quantify relative risks of internal tumor development for XP patients by tumor type, XP-subtype, patients' ages and ethnicity through comparison with the US general population. METHODS: We analyzed four independent international well-characterized XP cohorts (from USA, UK, France and Brazil) with a total of 434 patients, where 11.3% developed internal tumors and compared them to the American general population. We also compiled, through PubMed/Medline, a dataset of 89 internal tumors in XP patients published between 1958 and 2020. RESULTS: In the combined 4-XP cohort, relative risk of internal tumors was 34 (95% confidence interval (CI) 25-47) times higher than in the general population (p-value = 1.0E-47) and tumor arose 50 years earlier. The XP-C group was at the highest risk for the 0-20 years old-patients (OR = 665; 95% CI 368-1200; p-value = 4.3E-30). The highest risks were observed for tumors of central nervous system (OR = 331; 95% CI 171-641; p-value = 2.4E-20), hematological malignancies (OR = 120; 95% CI 77-186; p-value = 3.7E-36), thyroid (OR = 74; 95% CI 31-179; p-value = 1.2E-8) and gynecological tumors (OR = 91; 95% CI 42-193; p-value = 3.5E-12). The type of mutation on the XPC gene is associated with different classes of internal tumors. The majority of French XP-C patients (80%) are originated from North Africa and carried the XPC delTG founder mutation specific from the South Mediterranean area. The OR is extremely high for young (0-20 years) patients with more than 1300-fold increase for the French XPs carrying the founder mutation. CONCLUSION: Because the age of XP population is increasing due to better sun-protection and knowledge of the disease, these results are of particular importance for the physicians to help in early prevention and detection of internal tumors in their XP patients. Few preventive blood analyses or simple medical imaging may help to better detect early cancer appearance in this population.

Xeroderma Pigmentosum Associated with Squamous and Basal Cell Carcinoma in Pakistan: A Case Series.

ABSTRACT: Xeroderma pigmentosum (XP) is an autosomal recessive condition characterized by an extreme sensitivity to UV rays from sunlight. It presents clinically with progressive pigmentary abnormalities and an increased incidence of skin and mucous membrane cancers at sun-exposed sites. Parental consanguinity is a significant risk factor. Previously, cases of XP have been reported from various regions of Pakistan including Larkana, Sibbi, Karachi, Lahore, and District Dir in 1993, 2009, and 2010. Genetic studies have been conducted on seven consanguineous families with XP belonging to the Khosa tribe of Baloch ethnicity. In May 2018, XP was reported in four siblings in a family from a small village in Sindh Province, Pakistan. Current surveillance has been carried out in the tribal village of Lundi Khosa, District Kachhi at Baluchistan, Pakistan. The disease has been endemic in the tribe since 1986, although it was brought under control in the last few years. This case report describes five patients (aged 3-12 years) with XP who have developed nonmelanoma skin malignancies.

Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins.

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migration flows. Clinical and genetic profiling improves diagnosis, management, counselling, and implementation of future targeted therapies.

Outcomes of keratoplasty in a cohort of Indian patients with xeroderma pigmentosum.

Purpose: To evaluate the outcomes of keratoplasty for xeroderma pigmentosum (XP) performed at a tertiary eye care center. Methods: A retrospective review of medical records of those patients who were clinically diagnosed to have XP (54 eyes of 36 patients) and underwent keratoplasty; either deep anterior lamellar keratoplasty (DALK, four eyes), endothelial keratoplasty (EK, eight eyes), or penetrating keratoplasty (PK, 42 eyes) from 1994 to 2018. Results: The median age at surgery was 20.6 years (interquartile range [IQR], 14.6-27.6 years) and 20 (55.6%) were males. Graft failure occurred in 15 eyes (35.7%) in the PK group and two eyes (50%) in the DALK group; none failed in the EK group. The probability of graft survival in the PK group was 97.2% ± 2.7% at 1 year, 74.0% ± 8.0% at 2 years, and 54.8% ± 11.7% at 5 years. In the PK group, 13 eyes needed antiglaucoma medications, 11 eyes developed graft infiltrate, and 13 eyes needed secondary interventions (cataract surgery, excision biopsy, and tarsorrhaphy). In the EK group, three eyes needed secondary interventions (excision biopsy). Median postoperative endothelial cell density at the last follow-up in the PK group was 1214 cells/mm2 (IQR, 623-2277 cells/mm2). Conclusion: Despite the complexities of the ocular surface and adnexal issues in XP, keratoplasty had reasonably good outcomes. More than half of the PK grafts survived 5 years with no failures in the EK group. Regular follow-up and timely management of suture-related infections raised intraocular pressure, and suspicious ocular surface lesions, in addition to solar protection, are important for the success of keratoplasty in these eyes.

Xeroderma pigmentosum in Yemen.

BACKGROUND: The incidence of xeroderma pigmentosum (XP) in Yemen seems to be quite high but there are no previous reports. OBJECTIVE: To study the clinicoepidemiologic aspect of XP in Yemen. METHODS: All 40 patients (24 male and 16 female patients from 32 families) treated and followed between 1997 and 2014 were subjected to detailed analysis with the help of a standardized protocol. The diagnosis was based on clinical features and histopathologic data, when needed. The diagnosis of tumors was confirmed by histopathologic examination in all cases. RESULTS: The median age of onset of initial manifestations was 9.5 months, and that of malignant lesions was 7 years. Parents of the patients were not affected, but history of consanguinity was recorded in 38. Initial lesions, such as dryness of the skin and freckles on the face, were noticed in all patients. In addition, erythema of the face with photosensitivity was observed in 21 patients. Premalignant and malignant skin lesions observed later were actinic keratosis in 15 patients, lentigo maligna in one, squamous cell carcinoma (SCC) in 10, and basosquamous carcinoma in one. Eyes were affected with SCC in seven and malignant melanoma (MM) in two patients. SCC of the lip developed in two patients and that of the tongue in one patient. Judicious use of acitretin in 12 patients showed good result. CONCLUSION: XP in Yemen is characterized by a relatively high incidence, high percentage of consanguinity in parents of the patients, early onset of initial manifestations, malignant tumors, and severe ocular and oral lesions. Acitretin showed good result.

Ocular surface biopsies of patients with xeroderma pigmentosum in the United Kingdom: a retrospective observational case series.

BACKGROUND/AIMS: To describe the results of all ocular surface biopsies performed on patients with xeroderma pigmentosum (XP) under the care of the UK Nationally Commissioned XP Service as well as the treatment of any subsequent ocular surface conditions diagnosed. METHODS: Retrospective analysis of medical records. All patients with XP seen by the service from 2010 to 2019 were included and those with ocular surface biopsies were identified. Data was collected on demographics, complementation subgroup (A-G and V), biopsy details, histopathological analysis and subsequent management. RESULTS: Of 108 patients seen in our service, 17 underwent at least one ocular surface biopsy. 45 biopsy samples were available from 13 patients of which 65% were performed on patients from complementation subgroup C (XP-C). Biopsies were categorised as either non-mapping (clinically abnormal ocular surface tissue) or mapping (multiple sites including clinically normal tissue). 67 percent of non-mapping biopsies had a mass as their indication and 46% showed ocular surface squamous neoplasia. General non-dysplastic damage was seen in 67% of non-mapping biopsies and melanocytic changes were seen in 25% of non-mapping and 81% of mapping biopsies. 47 percent of biopsy outcomes required no additional treatment but, of those that did, 50% received mitomycin C. CONCLUSIONS: This is the largest reported series of ocular surface biopsies in patients with XP. It identifies a background of ocular surface melanocytic, degenerative and inflammatory changes, with patients with XP-C showing the most severe effects. We highlight challenges faced in interpreting their histopathology and in planning subsequent treatments.

Ocular Features in a Large Cohort of Indians With Xeroderma Pigmentosum.

PURPOSE: Xeroderma pigmentosum (XP) is an extreme hypersensitivity to sunlight causing skin freckling and pigmentary changes because of defective DNA repair mechanisms. The purpose of this article is to evaluate the spectrum of ocular and systemic features in XP at a tertiary eye care center in India over 32 years. METHODS: Data from 418 eyes of 209 patients diagnosed with XP from 1987 to 2018 were reviewed retrospectively for demographics, complaints, ocular features, systemic associations, and their management. RESULTS: Median age at diagnosis was 2 years (interquartile range, 0.5-5 years). A total of 124 patients (59.3%) were men. There was parental consanguinity in 74.4% cases. Common ocular complaints were photophobia (47.1%), ocular discomfort (45%), defective vision (36.6%), redness (13.4%), tissue growth (12%), white spot (11.2%), and pain (10.5%). At presentation, 43.5% had corneal scars (45.5% were located inferiorly and 70.9% covered visual axis). Corneal vascularization and limbal stem cell deficiency were noted in 37.4%. A total of 56% of patients had at least 1 tumor, and 6.7% had neurological abnormalities. At least 1 ocular surgery was performed in 37.8% of patients. Ophthalmic surgical interventions included tumor excision (23%), keratoplasty (13.4%), and nontumor ocular surface surgery (3.4%). CONCLUSIONS: XP is a disorder that has high ocular morbidity in Indian patients. The recognition of common signs and symptoms and relative frequency of various ocular complications with time trends will help in managing and reducing the sequelae of this otherwise untreatable and progressive disease.

The Iberian legacy into a young genetic xeroderma pigmentosum cluster in central Brazil.

In central Brazil, in the municipality of Faina (state of Goiás), the small and isolated village of Araras comprises a genetic cluster of xeroderma pigmentosum (XP) patients. The high level of consanguinity and the geographical isolation gave rise to a high frequency of XP patients. Recently, two founder events were identified affecting that community, with two independent mutations at the POLH gene, c.764 + 1 G > A (intron 6) and c.907 C > T; p.Arg303* (exon 8). These deleterious mutations lead to the xeroderma pigmentosum variant syndrome (XP-V). Previous reports identified both mutations in other countries: the intron 6 mutation in six patients (four families) from Northern Spain (Basque Country and Cantabria) and the exon 8 mutation in two patients from different families in Europe, one of them from Kosovo. In order to investigate the ancestry of the XP patients and the age for these mutations at Araras, we generated genotyping information for 22 XP-V patients from Brazil (16), Spain (6) and Kosovo (1). The local genomic ancestry and the shared haplotype segments among the patients showed that the intron 6 mutation at Araras is associated with an Iberian genetic legacy. All patients from Goiás, homozygotes for intron 6 mutation, share with the Spanish patients identical-by-descent (IBD) genomic segments comprising the mutation. The entrance date for the Iberian haplotype at the village was calculated to be approximately 200 years old. This result is in agreement with the historical arrival of Iberian individuals at the Goiás state (BR). Patients from Goiás and the three families from Spain share 1.8 cM (family 14), 1.7 cM (family 15), and a more significant segment of 4.7 cM within family 13. On the other hand, the patients carrying the exon 8 mutation do not share any specific genetic segment, indicating an old genetic distance between them or even no common ancestry.

Use of Big Data to Estimate Prevalence of Defective DNA Repair Variants in the US Population.

Importance: Wide use of genomic sequencing to diagnose disease has raised concern about the extent of genotype-phenotype correlations. Objective: To correlate disease-associated allele frequencies with expected and reported prevalence of clinical disease. Design, Setting, and Participants: Xeroderma pigmentosum (XP), a recessive, cancer-prone, neurocutaneous disorder, was used as a model for this study. From January 1, 2017, to May 4, 2018, the Human Gene Mutation Database and a cohort of patients at the National Institutes of Health were searched and screened to identify reported mutations associated with XP. The clinical phenotype of these patients was confirmed from reports in the literature and National Institutes of Health medical records. The genetically predicted prevalence of disease based on frequency of known pathogenic mutations was compared with the prevalence of patients clinically diagnosed with phenotypic XP. Exome sequencing of more than 200 000 alleles from the Genome Aggregation Database, the National Cancer Institute Division of Cancer Epidemiology and Genetics database of healthy controls, and an Inova Hospital Study database was used to investigate the frequencies of these mutations in the general population. Main Outcomes and Measures: Listing of all reported mutations associated with XP, their frequencies in 3 large exome sequence databases, determination of the number of patients in the United States with XP using modeling equations, and comparison of the observed and reported numbers of patients with XP with specific mutations. Results: A total of 156 pathogenic missense and nonsense mutations associated with XP were identified in the National Institutes of Health cohort and the Human Gene Mutation Database. The Genome Aggregation Database provided frequency data for 65 of these mutations, with a total allele frequency of 1.13%. The XPF (ERCC4) mutation, p.P379S, had an allele frequency of 0.4%, and the XPC mutation, p.P334H, had an allele frequency of 0.3%. With the Hardy-Weinberg equation, it was determined that there should be more than 8000 patients who are homozygous for these mutations in the United States. In contrast, only 3 patients with XP were reported as having the XPF mutation, and 1 patient was reported as having the XPC mutation. Conclusions and Relevance: The findings from this study suggest that clinicians should approach large genomic databases with caution when trying to correlate the clinical implications of genetic variants with the prevalence of disease risk. Unsuspected mutations in known genes with a predisposition for skin cancer may be responsible for some of the high frequency of skin cancers in the general population.

Ocular and Periocular Tumors in Xeroderma Pigmentosum: A Study of 120 Asian Indian Patients.

PURPOSE: We studied the incidence, treatment, and outcome of ocular and periocular tumors in patients with xeroderma pigmentosum (XP). DESIGN: Retrospective case series. METHODS: This single-institution study included 120 patients with XP who underwent intervention with excisional biopsy, enucleation, or orbital exenteration. The primary outcome measures were the occurrence of eyelid or ocular surface tumor, globe salvage, locoregional and systemic metastasis, and death. RESULTS: The mean age at presentation was 19 years. A family history of XP was present in 32 (27%) patients. Over a mean follow-up of 61 months, 34 (28%) patients developed no ocular/adnexal tumor, 86 (72%) developed ocular surface malignancy, 15 (13%) developed eyelid malignancy, and 22 (18%) developed other head and neck malignancies. Of the 86 patients with ocular surface malignancy, 48 (56%) had unilateral tumor and 38 (44%) had bilateral tumors. Invasive squamous cell carcinoma (n = 51, 41%) was the most common ocular surface tumor. Of the 15 patients with eyelid tumors, 14 (93%) had unilateral tumor and 1 (7%) had bilateral involvement. Basal cell carcinoma (n = 8, 50%) was the most common eyelid tumor. There were events of ocular surface tumor recurrence (n = 55 eyes, 44%), eyelid tumor recurrence (n = 5 eyes, 31%), locoregional lymph node metastasis (n = 3, 2%), systemic metastasis (n = 1, 1%), and death (n = 1, 1%). Overall, globe salvage was achieved in 119 (99%) patients (both eyes were salvaged in 92 [76%] patients and at least 1 eye was salvaged in 27 [23%] patients). CONCLUSION: XP is frequently associated with ocular surface, eyelid, and other head and neck malignancies. Lifelong follow-up is mandatory in these patients.

Characteristics of Xeroderma Pigmentosum in Japan: Lessons From Two Clinical Surveys and Measures for Patient Care.

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun-exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. In Japan, the frequency of the XP complementation group A is the highest, followed by the variant type; while in the Western countries, those of groups C or D are the highest. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that afflicted patients with XP, followed by squamous cell carcinoma, and malignant melanoma. The frequency of these skin cancers in patients with XP has decreased in these 20 years, and the age of onset of developing skin cancers is higher than those previously observed, owing to early diagnosis and education to patients and care takers on strict prevention from sunlight for patients with XP. On the other hand, the effective therapy for neurological XP has not been established yet, and this needs to be done urgently.

A novel frameshift mutation in the XPC gene in a Moroccan patient: a case report.

BACKGROUND: Xeroderma pigmentosum is an autosomal recessive inherited disease. The diagnosis is essentially based on clinical findings and the family history. This genodermatosis is genetically heterogeneous; to date, nine genes have been associated to this disorder. Based on the result of many studies, xeroderma pigmentosum complementation group C is the most common form of xeroderma pigmentosum. A founder mutation in the XPC gene was reported in the Maghreb region of northern Africa. According to these findings, the Department of Medical Genetics in Rabat offers molecular diagnosis by screening for the recurrent mutation c.1643_1644delTG which represents 74% of all the probands with xeroderma pigmentosum. CASE PRESENTATION: We describe the case of a 21-year-old Moroccan son of consanguineous parents diagnosed with xeroderma pigmentosum on the basis of sun-exposed skin abnormalities and bilateral ocular involvement. A molecular study led to the identification of a new frameshift insertion of four nucleotides in exon 9. CONCLUSIONS: To the best of our knowledge, this mutation has not been described. The sequencing of the ninth exon should be proposed as first line molecular analysis for all Moroccan patients with xeroderma pigmentosum.

Xeroderma pigmentosum-Cockayne syndrome complex.

Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical description of the syndrome. We also drew on clinical practices used in XP and in Cockayne syndrome without XP to aid management of XP-CS.Extensive searches of the literature identified 43 XP-CS patients. The diagnosis had been confirmed with molecular or biochemical methods in 42 of them. Clinical features of each patient were summarized in spreadsheets and summary statistics were generated from this data. XP patients are classified into complementation groups according to the gene that is mutated. There are four groups in XP-CS, and classification was available for 42 patients. Twenty-one were in the XP-G complementation group, 13 in XP-D, 5 in XP-B, and 3 in XP-F. Overall, the clinical features of XP-CS are very similar to those of CS without XP, with the exception of skin cancers in XP-CS. However, one intriguing finding was that cancer incidence was lower in XP-CS compared to XP alone or XP-neurological disorder. The cancer rate in XP-CS was higher than in CS without XP, an unsurprising finding. There is preliminary evidence for the existence of severity groups in XP-CS, as is the case in CS.Although health problems in XP-CS vary both in severity and in when they the first occur, there was overall homogeneity between all complementation groups and putative severity groups. Severely affected patients met fewer milestones and died at younger ages compared to more mildly affected patients.

Clinical and molecular epidemiological study of xeroderma pigmentosum in China: A case series of 19 patients.

Xeroderma pigmentosum (XP) is a rare genetic disorder which is divided into eight complementation groups: XP-A to XP-G and XP-V. Some XP patients demonstrate severe cutaneous and neurological manifestations, management of which requires timely diagnosis and intervention. We performed clinical evaluation and genetic analysis on 19 patients, the largest cohort of XP to date in China. Twenty-three mutations from six groups were identified, 16 of which were novel. All patients developed marked freckle-like pigmentation on sun-exposed sites while patients with XP-A, XP-D, XP-F and XP-G showed acute sunburn reactions. Only XP-A patients displayed progressive neurological degeneration. A relatively larger proportion of XP-A and XP-C were found in Chinese XP patients. One XP case and two carriers were prenatally determined. This study extended the mutation spectrum of XP in China and may aid in the diagnosis and treatment of Chinese XP patients.

Epidemiological trends and clinicopathological features of cutaneous melanoma in sporadic and xeroderma pigmentosum Tunisian patients.

BACKGROUND: Epidemiological features and trends of cutaneous melanoma (CM) in North-African populations remain unclear. Those populations are of particular interest as they belong to a mosaic of various other origins (sub-Saharan, European Ancestry, and North-African Berbers). The aim of this study is to draw epidemiological profile and clinicopathological features of CM in the Tunisian population. METHODS: Incidence analyses were based on data from regional cancer registries. Clinical data were collected from dermatological departments and xeroderma pigmentosum (XP) referral centers and provided CM clinicopathological characteristics and progression. Statistical analyses were achieved using R packages and SPSS 20.0. RESULTS: The incidence of CM in Tunisia is relatively low (0.5-0.7 per 100,000 inhabitants per year). Gender differences were observed regarding anatomical distribution (P = 0.004). Acral lentiginous melanoma (ALM) was the most frequent histological subtype (32.3%); however, nodular melanoma (NM) was the most aggressive and responsible for 54.8% of deaths. CM in XP patients develops at a median age that is 42 years earlier than sporadic cases, with preferential localization on the head and neck (P < 0.001). Finally, male patients exhibited survival disadvantages compared with females (adjusted hazard ratio (HR) = 2.22, 95% CI: 1.05-4.68, P = 0.037). CONCLUSIONS: Cutaneous melanoma features in Tunisia are closer to those of non-Caucasians, even though gender differences that are similar to those observed in Caucasians were uncovered. This study also emphasizes the aggressiveness of NM and its effect on melanoma patient deaths. Xeroderma pigmentosum stands as the major predisposing host factor.