Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C
A 17-year-old female Korean patient (XP115KO) was previously diagnosed with Xeroderma pigmentosum group C (XPC) by Direct Sanger sequencing, which revealed a homozygous nonsense mutation in the <i>XPC</i> gene (rs121965088: c.1735C > T, p.Arg579Ter). While rs121965088 is associated wi...
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MDPI AG
2023-04-01
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| author | Ji-In Seo Chikako Nishigori Jung Jin Ahn Jae Young Ryu Junglok Lee Mu-Hyoung Lee Su Kang Kim Ki-Heon Jeong |
| author_facet | Ji-In Seo Chikako Nishigori Jung Jin Ahn Jae Young Ryu Junglok Lee Mu-Hyoung Lee Su Kang Kim Ki-Heon Jeong |
| author_sort | Ji-In Seo |
| collection | DOAJ |
| description | A 17-year-old female Korean patient (XP115KO) was previously diagnosed with Xeroderma pigmentosum group C (XPC) by Direct Sanger sequencing, which revealed a homozygous nonsense mutation in the <i>XPC</i> gene (rs121965088: c.1735C > T, p.Arg579Ter). While rs121965088 is associated with a poor prognosis, our patient presented with a milder phenotype. Hence, we conducted whole-exome sequencing in the patient and her family members to detect coexisting mutations that may have resulted in a milder phenotype of rs121965088 through genetic interaction. <i>Materials and Methods</i>: the whole-exome sequencing analysis of samples obtained from the patient and her family members (father, mother, and brother) was performed. To identify the underlying genetic cause of XPC, the extracted DNA was analyzed using Agilent’s SureSelect XT Human All Exon v5. The functional effects of the resultant variants were predicted using the SNPinfo web server, and structural changes in the XPC protein using the 3D protein modeling program SWISS-MODEL. <i>Results</i>: Eight biallelic variants, homozygous in the patient and heterozygous in her parents, were detected. Four were found in the <i>XPC</i> gene: one nonsense variant (rs121965088: c.1735C > T, p.Arg579Ter) and three silent variants (rs2227998: c.2061G > A, p. Arg687Arg; rs2279017: c.2251-6A > C, intron; rs2607775: c.-27G > C, 5′UTR). The remaining four variants were found in non-XP genes, including one frameshift variant [rs72452004 of olfactory receptor family 2 subfamily T member 35 (<i>OR2T35</i>)], three missense variants [rs202089462 of ALF transcription elongation factor 3 (<i>AFF3</i>), rs138027161 of TCR gamma alternate reading frame protein (<i>TARP</i>), and rs3750575 of annexin A7 (<i>ANXA7</i>)]. <i>Conclusions</i>: potential candidates for genetic interactions with rs121965088 were found. The rs2279017 and rs2607775 of XPC involved mutations in the intron region, which affected RNA splicing and protein translation. The genetic variants of <i>AFF3</i>, <i>TARP</i>, and <i>ANXA7</i> are all frameshift or missense mutations, inevitably disturbing the translation and function of the resultant proteins. Further research on their functions in DNA repair pathways may reveal undiscovered cellular relationships within xeroderma pigmentosum. |
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| spelling | doaj.art-be7ceb9190ff4f1d87b36dadea47d9352023-11-17T20:20:42ZengMDPI AGMedicina1010-660X1648-91442023-04-0159469910.3390/medicina59040699Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group CJi-In Seo0Chikako Nishigori1Jung Jin Ahn2Jae Young Ryu3Junglok Lee4Mu-Hyoung Lee5Su Kang Kim6Ki-Heon Jeong7Department of Dermatology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDivision of Dermatology, Internal Related, Graduate School of Medicine, Kobe University, Kobe 653-0002, JapanDepartment of Oral Anatomy and Developmental Biology, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Oral Anatomy and Developmental Biology, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Dermatology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biomedical Laboratory Science, Catholic Kwandong University, Gangneung 25601, Republic of KoreaDepartment of Dermatology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaA 17-year-old female Korean patient (XP115KO) was previously diagnosed with Xeroderma pigmentosum group C (XPC) by Direct Sanger sequencing, which revealed a homozygous nonsense mutation in the <i>XPC</i> gene (rs121965088: c.1735C > T, p.Arg579Ter). While rs121965088 is associated with a poor prognosis, our patient presented with a milder phenotype. Hence, we conducted whole-exome sequencing in the patient and her family members to detect coexisting mutations that may have resulted in a milder phenotype of rs121965088 through genetic interaction. <i>Materials and Methods</i>: the whole-exome sequencing analysis of samples obtained from the patient and her family members (father, mother, and brother) was performed. To identify the underlying genetic cause of XPC, the extracted DNA was analyzed using Agilent’s SureSelect XT Human All Exon v5. The functional effects of the resultant variants were predicted using the SNPinfo web server, and structural changes in the XPC protein using the 3D protein modeling program SWISS-MODEL. <i>Results</i>: Eight biallelic variants, homozygous in the patient and heterozygous in her parents, were detected. Four were found in the <i>XPC</i> gene: one nonsense variant (rs121965088: c.1735C > T, p.Arg579Ter) and three silent variants (rs2227998: c.2061G > A, p. Arg687Arg; rs2279017: c.2251-6A > C, intron; rs2607775: c.-27G > C, 5′UTR). The remaining four variants were found in non-XP genes, including one frameshift variant [rs72452004 of olfactory receptor family 2 subfamily T member 35 (<i>OR2T35</i>)], three missense variants [rs202089462 of ALF transcription elongation factor 3 (<i>AFF3</i>), rs138027161 of TCR gamma alternate reading frame protein (<i>TARP</i>), and rs3750575 of annexin A7 (<i>ANXA7</i>)]. <i>Conclusions</i>: potential candidates for genetic interactions with rs121965088 were found. The rs2279017 and rs2607775 of XPC involved mutations in the intron region, which affected RNA splicing and protein translation. The genetic variants of <i>AFF3</i>, <i>TARP</i>, and <i>ANXA7</i> are all frameshift or missense mutations, inevitably disturbing the translation and function of the resultant proteins. Further research on their functions in DNA repair pathways may reveal undiscovered cellular relationships within xeroderma pigmentosum.https://www.mdpi.com/1648-9144/59/4/699xeroderma pigmentosum group Cwhole exome sequencingbioinformatics analysisXPC |
| spellingShingle | Ji-In Seo Chikako Nishigori Jung Jin Ahn Jae Young Ryu Junglok Lee Mu-Hyoung Lee Su Kang Kim Ki-Heon Jeong Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C Medicina xeroderma pigmentosum group C whole exome sequencing bioinformatics analysis XPC |
| title | Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C |
| title_full | Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C |
| title_fullStr | Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C |
| title_full_unstemmed | Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C |
| title_short | Whole Exome Sequencing of a Patient with a Milder Phenotype of Xeroderma Pigmentosum Group C |
| title_sort | whole exome sequencing of a patient with a milder phenotype of xeroderma pigmentosum group c |
| topic | xeroderma pigmentosum group C whole exome sequencing bioinformatics analysis XPC |
| url | https://www.mdpi.com/1648-9144/59/4/699 |
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