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

Abstract

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.

Keywords: Case Report; Melanoma; XP-E; Xeroderma Pigmentosum.

Fig. 1

A Pedigree of the family showing consanguineous marriage. Both parents (I.1 and I.2) are heterozygous for NM_000107.3:c.1027G > C and patient ID_4.19 (II.4) and patient ID_4.20 (II.3) are homozygous for this variant. The two older siblings are asymptomatic and were not tested. B Reverse sequence electropherogram from mother and father of siblings. The NM_000107.3:c.1027G > C variant is highlighted in red. C Reverse sequence electropherogram from ID_4.19 and ID_4.20. D Photos to evidence severe phenotype. Patient ID_4.19 1. Photo from exeresis to remove lesions in lips, face and nose. 2 and 3. Photo of the nodular, pigmented and elevated lesion of the LE, extending throughout the cornea. 4. Photo showing the melanoma of the RE. Patient ID_4.20 5. Photo showing lesions that were removed and pigmentation on the back, exposed to sunlight. 6. Photo from exeresis of the lesion located in the right parotid gland, before surgery and 7. After the total parotidectomy. E Milestones of patient’s clinical history, Patient ID_4.19 is highlighted in blue and for Patient ID_4.20, in orange, unfortunately, he passed away on 12/06/2022

Fig. 2

Genetic analysis of the WES. A XP-E patients ROH regions detected at each chromosome. The regions highlighted in blue and in red refer to ROH in Patient ID_4.20 and Patient ID_4.19, respectively. B DDB2 gene schematic representation and pathogenic variants and VUS described in databases. The exons are in yellow, all variants submitted at ClinVar and described in literature are listed (reviewed by Yang and coworkers, 2020 [26] and the variant detected in the two siblings is highlighted in red