Repository of Research and Investigative Information

Repository of Research and Investigative Information

دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

GATA4 screening in Iranian patients of various ethnicities affected with congenital heart disease: Co-occurrence of a novel de novo translocation (5;7) and a likely pathogenic heterozygous GATA4 mutation in a family with autosomal dominant congenital heart disease

(2019) GATA4 screening in Iranian patients of various ethnicities affected with congenital heart disease: Co-occurrence of a novel de novo translocation (5;7) and a likely pathogenic heterozygous GATA4 mutation in a family with autosomal dominant congenital heart disease. J Clin Lab Anal. e22923. ISSN 0887-8013

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Official URL: https://pubmed.ncbi.nlm.nih.gov/31115957/

Abstract

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect and a major health problem around the world. However, its exact etiology has remained unclear. Among various genetic contributing factors, GATA4 transcription factor plays a significant role in the CHD pathogenesis. In this study, GATA4 coding sequence was screened in Iranian patients of various ethnicities. METHODS: Sixty six individuals with familial CHD referred to our center were recruited in this study. After receiving written informed consent from each individual or their parents, chromosomal analyses and GATA4 variant screening were performed. Pathogenicity of the suspected variants was evaluated using available online software tools: CADD, Mutation Taster, SIFT, and PolyPhen-2. RESULTS: A total of twelve GATA4 variants were detected including five intronic, 2 exonic and 3 polymorphisms as well as 2 missense mutations, the c.1220C\textgreaterA and c.1309G\textgreaterA. Unlike the c.1220C\textgreaterA, the likely pathogenic heterozygous c.1309G\textgreaterA has not been previously associated with any phenotype. Here, we not only report, for the first time, a c.1309G\textgreaterA-related CHD, but also report a novel de novo balanced translocation, 46,XY,t(5;7)(qter13;qter11), in the same patient which may have influenced the disease severity. CONCLUSION: From screening GATA4 sequence in 66 Iranian patients of various ethnicities, we conclude that cytogenetic analysis and PCR-direct sequencing of different candidate genes may not be the best approach for genetic diagnosis in CHD. Applying novel approaches such as next-generation sequencing (NGS) may provide a better understating of genetic contributing factors in CHD patients for whom conventional methods could not reveal any genetic causative factor.

Item Type: Article
Keywords: *Genes, Dominant,*Translocation, Genetic,Adolescent,Adult,Amino Acid Sequence,Base Sequence,Cytogenetic Analysis,Ethnic Groups/*genetics,Family,Female,GATA4 Transcription Factor/chemistry/*genetics,GATA4 gene,Heart Defects, Congenital/diagnostic imaging/*genetics,Heterozygote,Humans,Iran,Male,Middle Aged,Mutation/*genetics,Pedigree,congenital heart disease,karyotyping,whole-exome sequencing
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
Cardiovascular System > WG 200-460 Heart. Heart Diseases
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Molecular Medicine and Genetics
Page Range: e22923
Journal or Publication Title: J Clin Lab Anal
Abstract and Indexing: ISI, Pubmed, Scopus
Quartile : Q3
Volume: 33
Number: 7
Publisher: Wiley ,ProQuest
Identification Number: https://doi.org/10.1002/jcla.22923
ISSN: 0887-8013
ISBN: 0887-8013
Depositing User: خانم فائزه مظفری
URI: http://repository.zums.ac.ir/id/eprint/5560

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