Search

Objective: Atrial septal defect (ASD) is one of the most common types of congenital heart disease (CHD). It is mainly caused by mutations of NK2 homeobox 5, GATA binding protein 4 (GATA4), and myosin heavy chain 6 in non-syndromic cases. This study aims to carry out, for the first time, the GATA4 mutation screening in a Moroccan population affected by ASD and compare the obtained mutation rate across populations., Materials and Methods: A total of 33 patients were enrolled in this study. DNAs were extracted from peripheral blood samples, and we performed PCR-sequencing for GATA4 coding regions. Sequences were analyzed by sequence alignment and functional impact prediction tools. Mutation rate comparisons were performed by R software using the appropriate statistical tests., Results: We detected 7 variants, but no pathogenic mutation was revealed, except for Asn352= that was assessed by human splicing finder algorithms to have a potential impairing effect on the splicing mechanism. Until proven by in vitro functional studies, the current pathogenic mutation rate in our cohort seems to be 0%. Statistical comparison with previous studies from all over the world shows no significant difference. Seemingly, comparison of previous GATA4 mutation rates among tetralogy of Fallot (TOF) populations shows no significant difference., Conclusion: The low rates of GATA4 mutations observed throughout ASD and TOF international populations may suggest a limited causality of GATA4 mutations in the main CHDs, which further confirms the co-involvement of additional genetic and/or environmental factors in the manifestation of these phenotypes., Competing Interests: Conflict of Interest: Authors have no conflicts of interest to declare., (©Copyright 2020 by the Atatürk University School of Medicine - Available online at www.eurasianjmed.com.)

Lynch syndrome (LS) is an autosomal dominant disorder characterized by an increased risk of extracolonic cancers and early age of onset. It is associated with germline mutations in the DNA mismatch repair (MMR) genes. We report a case of a patient with colorectal cancer referred to our medical genetics department for molecular analysis and genetic counseling. The proband is a 64-year-old woman diagnosed with a tumor of the cecum. Histopathological examination showed a moderately differentiated mucinous adenocarcinoma categorized by pT3 N0. Analysis of her pedigree revealed three siblings who had colon cancer, as well as one relative with brain cancer. Based on these findings, molecular genetic investigation was found to be necessary in order to identify the disease-causing mutation. Immunohistochemistry staining of MMR proteins was performed on the tumor sample of the index proband. Mutational analysis of the MLH1/MSH2 genes was carried out. Analysis was extended to the family members and the general population. This led to the identification of a heterozygous frameshift duplication in the MLH1 gene at position 910 (c.910dupG). Three siblings had inherited the mutation from their mother, two of whom were asymptomatic at the time of diagnosis. To the best of our knowledge, this is a novel pathogenic duplication that has not been reported in the databases and literature. The outcome of the present case suggests that this mutation was the primary cause of LS in the family.