PMC6543889_01
The pedigrees of the patients.  affected male,  affected female,  unaffected male,  unaffected female, X mark: deceased.
fgene-10-00495-g001.jpg
PMC6543889_01_fgene-10-00495-g001.jpg
F1
The proband (Figure 1: IV:5) is a 36-year-old male who developed many pigmented freckle-like patches in the skin starting at 4 years of age. According to Swiss-Model, the protein model of DNA polymerase eta exhibits different lengths and configurations in the normal controls and patients with mutations in the POLH gene, suggesting significant functional deficiency (Supplementary Figure 1).
Clinical and histopathological appearance of hyperpigmentation. Hyperpigmented lesions on the face (a) and dorsal hand (b); melanin pigmentation in the basal layer and extension of the furcella into the dermis in a bud shape (c) HE stain, x 100; (d) HE stain, x 400.
fgene-10-00495-g002.jpg
PMC6543889_01_fgene-10-00495-g002.jpg
F2
These changes were particularly located in UV-exposed areas, such as the face (Figure 2a), upper thorax, upper limbs, dorsal hands (Figure 2b), feet and legs, and gradually worsened before 18 years of age, after which the condition stabilized. Histopathological examination of the skin lesions was performed and revealed melanin pigmentation in the basal layer and extension of the furcella into the dermis with a bud shape (Figure 2c,d).
Clinical and histopathological appearance of psoriasis. Lesions on the lower limbs (a) continuous parakeratosis and Munro microabscesses in the epidermal layer, dilated superficial vessels, and infiltration of a few lymphocytes in the dermis layer (b) HE stain, x 100.
fgene-10-00495-g003.jpg
PMC6543889_01_fgene-10-00495-g003.jpg
F3
The skin lesions were covered with thick scales that had characteristics of the wax droplet phenomenon, the membrane phenomenon and dotty hemorrhage (Figure 3a). The dermis layer exhibited dilated superficial vessels and infiltration of a few lymphocytes (Figure 3b).
Sanger sequencing of POLH and TCTE1. Normal control (IV:2, IV:3, IV:4, V2) (a), homozygous mutations (IV:1, IV:5) (b) and heterozygous mutations (III:1, III:2, V1) (c) of POLH (c.353dupA, p. Y118_V119delinsX); normal control (IV:2, IV:3, IV:4, V2) (d), homozygous mutations (IV:1, IV:5) (e) and heterozygous mutations (III:1, III:2, V1 (f) of TCTE1 (c. T214C, p. S72P). The mutational bases were arrowed.
fgene-10-00495-g004.jpg
PMC6543889_01_fgene-10-00495-g004.jpg
F4
S72P) were confirmed by Sanger sequencing and identified as being heterozygous in the patients' normal parents and another family member (III:1, III:2, V1; Figure 4c,f). They were both homozygous variants in the patients (IV:1, IV:5; Figure 4b,e). However, the variants were not found in the rest of the family (IV:2, IV:3, IV:4, V2; Figure 4a,d) and was not reported in the databases searched or previous genome-wide association studies.