PMC8203331_01
Pedigrees and clinical images describing two XP affected family members (XP21 and XP134) (A,B). Filled symbols represent affected individuals, open symbols represent unaffected individuals, gray symbols are for suspected individuals, the studied pro-band is indicated with an arrow.
fgene-12-650639-g0001.jpg
PMC8203331_02_fgene-12-650639-g0001.jpg
F1
PMC8203331_02
Pedigrees and clinical images describing two XP affected family members (XP21 and XP134) (A,B). Filled symbols represent affected individuals, open symbols represent unaffected individuals, gray symbols are for suspected individuals, the studied pro-band is indicated with an arrow.
fgene-12-650639-g0001.jpg
PMC8203331_02_fgene-12-650639-g0001.jpg
F1
Molecular findings: (A) Electropherogram showing the variation in ERCC4 gene in exon 8 (c.1762 G>T p.V588F) at a homozygous state in the patient XP21. (B) Electropherogram showing double variation in DDB2 gene (c.613 T>C p.C205R and c.618 C>A p.S206R) in exon 5 in XP134 patient. (C) Structures of the XPF protein and F588 XPF mutant suggesting a mild distortion in helix domain. (D) DNA DDB2 protein interaction for muted DDB2 protein suggestion that R206 affect this process.
fgene-12-650639-g0002.jpg
PMC8203331_02_fgene-12-650639-g0002.jpg
F2
Through targeted gene sequencing of 87 genes involved in NER pathway, we identified in patient XP21 a novel homozygous missense variation in ERCC4, within exon 8, (NM_005236.2 c.1762G>T p.Val588Phe) (Figure 2A). Regarding the patient XP134, we found that he carried a double homozygous missense variation in DDB2 gene in exon 5 (NM_000107.2: c.613T>C p.Cys205Arg) and c.618C>A p.Ser206Arg (rs759622121) (Figure 2B). In the case of V588F mutation causes steric clashes with L580 residue due to its large bulky side chain compared to a valine amino acid in the wild type form (Figure 2C). Its relatively long side chain is unable to interact with the deepest most residues forming the interface of two bladders (Residues V225, V245 and T260) which is not the case for S206 in the wild type form (Figure 2D).