Identification of a novel mutation in PLOG in a patient with Progressive external ophthalmoplegia: a case non report

Background and Aim: Progressive external ophthalmoplegia (PEO) with multiple deletions mitochondrial DNA (mtDNA) is associated with several mutations in nuclear gene. They include POLG, POLG۲, ANT۱, C۱۰ or F۲ ⁄ Twinkle and OPA۱. POLG is the only DNA polymerase responsible for mtDNA replication. MtDNA is replicated by DNA polymerase gamma (POLG) encoded by the nuclear POLG gene (OMIM#۱۷۴۷۶۳). The human POLG gene is located on chromosome ۱۵q۲۶.۱ and its cDNA comprises ۴.۴۶۵ bp. However digenic inheritance in mitochondrial disorders has been documented in a few cases over the years. In this disease inheritance is dominant in the form of autosomal.Methods: Here we describe a five-year-old girl who has been referred to us by a neurologist. Proband' parents are quite healthy and they are first cousins. Her mother has a completely natural pregnancy and childbirth. Proband has four years of natural status but with a sudden seizure the symptoms of the disease show that the most important is muscle weakness- progressive. As the first symptom, canbe called an involuntary of eye movements. Patient's symptoms are as follows: Exercise intolerance, Muscle weakness, Muscle atrophy, highly variable phenotype, Adult onset, Progressive disorder. According to these symptoms, the Mono (patient) Whole Exome Sequencing Test (WES) was performed on the patient's peripheral blood sample. Then, the mutations found in the WES tryout, were analyzed by Sanger- sequencing method on her parents and brother.Results: The results show a novel heterozygous mutation (c.C۲۸۲۷T, R۹۴۳C) in exon ۱۸ of the POLG gene.Conclusion: The outcome of the patient's parents is as follows: her father's genotype is homozygote but her mothers' is heterozygote. The disease is dominant, but her mother is completely healthy. That it shows incomplete penetration of disease while proband shows full penetration. Novel mutation causes great deletions in the mitochondrial gene and gradually with the accumulation of ineffective mitochondria; symptoms accessed and causes severe problems in the patient.

کلیدواژه ها:

POLG Gene ، PEO disease ، Mitochondrial disorders