Multidisciplinary Cancer Investigation

en Genetic Identification of a Novel Truncating Mutation p.Thr738Argfs*28 in XPC Gene in a Family from Iraq Genetics Case Report and Series <div style="text-align: justify;">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.</div> Xeroderma pigmentosum (XP), Genotyping Pathogenic mutation, Homology modeling, Genetic counseling 51 59 http://mcijournal.com/browse.php?a_code=A-10-286-2&slc_lang=en&sid=1 Fatemeh Yadegari yadegari1985@gmail.com 10031947532846004236 10031947532846004236 No Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Aseel Rashid Abed dr_abdas@yahoo.com 10031947532846004237 10031947532846004237 No Warith International Cancer Institute, Karbala, Iraq Widad Yadallah Abd Ali Widadi2007@yahoo.com 10031947532846004238 10031947532846004238 No Warith International Cancer Institute, Karbala, Iraq Haider Hamza Al-Abedi haydar.h@warith-ici.net 10031947532846004239 10031947532846004239 No Warith International Cancer Institute, Karbala, Iraq Shiva Zarinfam sh.zarinfam@gmail.com 10031947532846004240 10031947532846004240 No Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Rabbie Hanna r.hanna@warith-ici.net 10031947532846004241 10031947532846004241 No Warith International Cancer Institute, Karbala, Iraq Fawaz Al-Alloosh f.alalloosh@warith-ici.net 10031947532846004242 10031947532846004242 No Warith International Cancer Institute, Karbala, Iraq Solaleh Aminian s.aminian110@gmail.com 10031947532846004243 10031947532846004243 No Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran Keivan Majidzadeh-A kmajidzadeh@acecr.ac.ir 10031947532846004244 10031947532846004244 Yes Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran