Ghaedi Hamid, Ramsheh Samira Molaei, Omidvar Maryam Erfanian, Labbaf Afsaneh, Alehabib Elham, Akbari Sanaz, Pourfatemi Fatemeh, Darvish Hossein
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Laboratory Technology, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Genes Dis. 2019 Jul 27;7(4):614-619. doi: 10.1016/j.gendis.2019.07.011. eCollection 2020 Dec.
Hereditary nonpolyposis colorectal cancer or Lynch syndrome is autosomal dominant cancer predisposition syndrome characterized by early onset of colorectal cancer and neoplasia in other organs. This condition typically caused by germline mutations in the mismatch repair genes , , , and . To date, a considerable number of gene mutations have been found to be associated with Lynch syndrome. We were aimed at identifying a genetic mutation in an extended Iranian family affected by Lynch syndrome-related cancers. Here, we applied whole-exome sequencing to identifying mutation in the proband. Furthermore, we applied Sanger sequencing to validate the candidate variant. We found a heterozygous novel single nucleotide deletion (c.206delG) in the exon two of the gene in the proband. Also, Sanger sequencing analysis showed that this mutation has segregated in all affected family members. The mutation (c.206delG:p.R69fs) may create a premature stop codon followed by the formation of a truncated (p.R69fs) Mlh1 protein. Our findings expand the mutational spectra of gene related Lynch syndrome which is vital for screening and genetic diagnosis of the disease.
遗传性非息肉病性结直肠癌或林奇综合征是一种常染色体显性癌症易感综合征，其特征为结直肠癌发病早且其他器官出现肿瘤。这种情况通常由错配修复基因、、和中的种系突变引起。迄今为止，已发现相当数量的基因突变与林奇综合征相关。我们旨在鉴定一个受林奇综合征相关癌症影响的伊朗大家庭中的基因突变。在此，我们应用全外显子组测序来鉴定先证者中的突变。此外，我们应用桑格测序来验证候选变异体。我们在先证者的基因外显子2中发现了一个杂合的新型单核苷酸缺失（c.206delG）。此外，桑格测序分析表明该突变在所有受影响的家庭成员中均有分离。该突变（c.206delG:p.R69fs）可能会产生一个过早的终止密码子，随后形成截短的（p.R69fs）Mlh1蛋白。我们的发现扩展了与林奇综合征相关的基因的突变谱，这对于该疾病的筛查和基因诊断至关重要。
