Results of Mitochondrial DNA Sequence Analysis in Patients with Clinically Diagnosed Leber’s Hereditary Optic Neuropathy

Abstract

Objective: To investigate possible mitochondrial DNA (mtDNA) mutations in patients with Leber's hereditary optic neuropathy (LHON) in order to provide a precise diagnosis and genetic counseling. Material and Methods: Between 1982 and 2007, ten patients were clinically diagnosed with LHON and six of these patients agreed to be involved in this study. Six healthy individuals were also included as a control group. mtDNA was isolated from peripheral blood samples and polymerase chain reaction and mtDNA sequence analysis were performed. Results: In one of the six patients, a homoplasmic mutant m.11778G>A mutation was detected. All of the clinically diagnosed LHON patients and the control groups had the m.14212C>T and m.14580G>A single nucleotide polymorphisms (SNPs). The m.11719A>G SNP was detected in three of six patients and four of the controls. Two of the six patients had the m.3197T>C SNP and, in addition, the m.14258G>A SNP was found in one of these two patients, while neither of these mutations were present in the control group. Conclusion: The clinical diagnosis of LHON could be supported by molecular genetics only in one patient by the detection of one mutation. The m.3197T>C and m.14258G>A SNPs should be considered as potential mtDNA mutations due to the fact that they were detected in the patient group. These mutations should be investigated further in large case groups for suspected gene loci that could lead to optic neuropathy. Turkish Anahtar Kelimeler: Leber herediter optik nöropatisi, ailevi optik atrofi, mitokondrial DNA, Mıtokondrial DNA mutasyonları tek nükleotid polimorfizmi Amaç: Klinik olarak Leber'in Herediter Optik Nöropatisi (LHON) tanısı alan hastalarda, kesin tanı ve genetik danışmanlık verilebilmesi için olası mitokondriyal DNA mutasyonlarının araştırılması. Gereç ve Yöntemler: 1982-2007 yılları arasında klinik olarak LHON tanısı alan 10 hasta kliniğimize davet edildi. Bütün olgularda rutin oftalmolojik muayeneden sonra alınan periferik venöz kan örneklerinden mitokondriyal DNA ayrıştırılarak, polimeraz zincir reaksiyonu (PCR) ve mitokondriyal DNA dizi analizi yapıldı. Bulgular: 6 hastadan birinde Homozigot mutant olarak m.11778G>A tek nükleotid değişimi (SNP) saptandı. 12 olgunun hepsinde m.14212C>T ve m.14580G>A SNP bulundu. 6 hastanın üçünde saptadığımız m.11719A>G SNP, aynı zamanda kontrol grubundaki 4 kişide de saptandı. 6 hastanın ikisinde m.3197T>C SNP ve bunlardan birinde ayrıca m.14258G>A SNP bulunurken bu SNP'lerin hiçbirine kontrol grubunda rastlanmadı. Sonuç: Klinik olarak LHON tanısı alan olgularımızdan sadece birinde bilinen mutasyonlardan biri saptanarak klinik tanı moleküler genetik olarak da desteklendi. m.14258G>A SNP'nin optik nöropatiye yol açabilecek olası mitokondriyal DNA mutasyonu olabileceği öngörüsündeyiz. Bu hipotezimizin kesinlik kazanabilmesi için olgu ve kontrol grubu sayısının arttırılarak çalışılmasına ihtiyaç vardır.

Keywords

• : Leber’s hereditary optic neuropathy, familial optic atrophy, mitochondrial DNA, mitochondrial DNA mutations, single nucleotide polymorphism

Results of Mitochondrial DNA Sequence Analysis in Patients with Clinically Diagnosed Leber’s Hereditary Optic Neuropathy

Öz

Kaynakça

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