Multidisciplinary Cancer Investigation
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Multidiscip Cancer Investig 2025, 0 - Multidisciplinary Cancer Investigation: 51-59 |
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Ethics code: IR.ACECR.Avicenna.rec.1396.24
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Yadegari F, Rashid Abed A, Yadallah Abd Ali W, Hamza Al-Abedi H, Zarinfam S, Hanna R, et al . Genetic Identification of a Novel Truncating Mutation p.Thr738Argfs*28 in XPC Gene in a Family from Iraq. Multidiscip Cancer Investig 2025;
URL: http://mcijournal.com/article-1-411-en.html
URL: http://mcijournal.com/article-1-411-en.html
Fatemeh Yadegari1 
, Aseel Rashid Abed2 , Widad Yadallah Abd Ali2 , Haider Hamza Al-Abedi2 , Shiva Zarinfam1 , Rabbie Hanna2 , Fawaz Al-Alloosh2 , Solaleh Aminian1 , Keivan Majidzadeh-A *3
, Aseel Rashid Abed2 , Widad Yadallah Abd Ali2 , Haider Hamza Al-Abedi2 , Shiva Zarinfam1 , Rabbie Hanna2 , Fawaz Al-Alloosh2 , Solaleh Aminian1 , Keivan Majidzadeh-A *3
1- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
2- Warith International Cancer Institute, Karbala, Iraq
3- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran ,kmajidzadeh@acecr.ac.ir
2- Warith International Cancer Institute, Karbala, Iraq
3- Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran ,
Abstract: (859 Views)
Introduction: Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder characterized by extreme sensitivity to UV-induced DNA damage, resulting in symptoms such as severe sunburn, freckles, dry skin, premature skin aging, and, occasionally, neurological symptoms.
Case Report: The study focuses on a 6-year-old girl with XP symptoms since age three. Genotyping was performed to identify the responsible mutation, followed by molecular modeling to predict the structural consequences of the amino acid substitution.
Results: The identified variant is a novel homozygous frameshift mutation XPC: c.2213_2216del (p.Thr738Argfs*28) in exon 12, corresponding to genomic coordinates (hg19/GRCh37) chr3:14190347 CTCTG>C based on the canonical transcript NM_004628.5. This variant is predicted to cause XP. Homology modeling reveals that this mutation deletes a critical region at the extreme COOH terminus of the XPC protein, which is crucial for its interaction with TFIIH and CETN2. While the mutant protein can still interact with DNA, it loses its ability to interact with TFIIH and CETN2, leading to loss of protein function.
Conclusions: This study expands the spectrum of mutations observed in the XPC gene by identifying a new pathogenic mutation. The results of this study highlight the importance of medical and genetic counseling in protecting future generations against genetic disease.
Case Report: The study focuses on a 6-year-old girl with XP symptoms since age three. Genotyping was performed to identify the responsible mutation, followed by molecular modeling to predict the structural consequences of the amino acid substitution.
Results: The identified variant is a novel homozygous frameshift mutation XPC: c.2213_2216del (p.Thr738Argfs*28) in exon 12, corresponding to genomic coordinates (hg19/GRCh37) chr3:14190347 CTCTG>C based on the canonical transcript NM_004628.5. This variant is predicted to cause XP. Homology modeling reveals that this mutation deletes a critical region at the extreme COOH terminus of the XPC protein, which is crucial for its interaction with TFIIH and CETN2. While the mutant protein can still interact with DNA, it loses its ability to interact with TFIIH and CETN2, leading to loss of protein function.
Conclusions: This study expands the spectrum of mutations observed in the XPC gene by identifying a new pathogenic mutation. The results of this study highlight the importance of medical and genetic counseling in protecting future generations against genetic disease.
Keywords: Xeroderma pigmentosum (XP), Genotyping Pathogenic mutation, Homology modeling, Genetic counseling
Select article type: Case Report and Series |
Subject:
Genetics
Received: 2025/07/1 | Accepted: 2025/12/7 | ePublished: 2025/12/10
Received: 2025/07/1 | Accepted: 2025/12/7 | ePublished: 2025/12/10
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