A novel heterozygous mutation in theSDHD gene in an Iranian patient with pheochromocytoma

Background: Pheochromocytomas are catecholamine-secretingtumors that usually arise within the adrenal medulla. Approximately۱۰% arise in extraadrenal sympathetic ganglia,and are referred to as 'paragangliomas.' Approximately ۱۰%are malignant, and approximately ۱۰% are hereditary. Usually,a pheochromocytoma develops in only one adrenal gland. Buttumors can develop in both. Symptoms of pheochromocytomasoften include: high blood pressure, headache, heavy sweating,rapid heartbeat, tremors and shortness of breath.Pheochromocytomas are typically inherited in an autosomaldominant pattern and can be caused by germline and somaticmutations in several genes. However this phenotype most commonlyoccur as part of several syndromes, and mutations in thegenes that cause these syndromes have been identified in patientswho manifest only pheochromocytoma. Approximately۱۰ genes have been associated to pheochromocytoma, such asSDHD gene. This gene encodes an integral membrane proteinsubunit of the succinate dehydrogenase complex.Materials and Methods: A couple with one child with suspectedpheochromocytoma was referred to genetic counselingcenter. They had nonfamilial marriage without any evidence ofgenetic disorder in familial pedigree. Whole Exome Sequencing(WES) was used to enrich all exons of protein-coding genesas well as some important other genomic regions. Bioinformaticsanalysis of the sequencing results was performed using internationaldatabases and standard bioinformatics software. Weperformed sanger-sequencing in order to confirm the mutations.Results: A heterozygous deleterious mutation (c.۱۵۴-۱۶۱del:p.Ser۵۲ProfsTer۱۴) in SDHD gene (NM_۰۰۳۰۰۲.۴) was found inproband. This condition was not found in his parents.Conclusion: There was no report of this mutation in the literature.Mutation in this gene is shown to cause pheochromocytoma.Because pheochromocytoma is rarely cancerous andmay spread to other parts of the body, a quick diagnosis of thisdisease helps to treat the patient in time. Furthermore, this datacan be used for genetic counseling and prenatal diagnosis

کلیدواژه ها:

SDHD gene ، pheochromocytoma ، deleterious mutation ، Whole Exome Sequencing (WES)