Turkiye Klinikleri Journal of Medical Sciences

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Miyotonik Distrofi Hastalarının CTG Tekrar Sayıları ile Genotip ve Klinik Bulguların Değerlendirilmesi: Tek Merkez Deneyimi-Olgu Serisi
Evaluation of CTG Repeat Numbers, Genotype and Clinical Findings in Myotonic Dystrophy Patients: A Single Center Experience-Case Series
Serap TUTGUN ONRATa, Muhsin ELMASa, Ümit Can YILDIRIMa, Hayri DEMİRBAŞb
aAfyonkarahisar Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Tıbbi Genetik ABD, Afyonkarahisar, TÜRKİYE
bAfyonkarahisar Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Nöroloji ABD, Afyonkarahisar, TÜRKİYE
Turkiye Klinikleri J Med Sci. 2021;41(3):298-304
doi: 10.5336/medsci.2021-82942
Article Language: TR
Full Text
ÖZET
 Amaç: Miyotonik distrofi hastalığı (MD), otozomal dominant genetik geçiş özelliği gösteren, motor, psikiyatrik ve bilişsel içerikli klinik bulgularla karakterize, CTG tekrar dizisi artışıyla ilerleyici nörodejeneratif bir hastalıktır. Kromozom 19'un uzun kolunda lokalize (19q13.32) miyotonin-protein kinaz olarak da bilinen miyotonik distrofi protein kinaz ya da distrofi miyotonika protein kinaz (DMPK) geni (Chr19:45,769,717-45,782,552-ENSG00000104936) düz, iskelet ve kalp kasında eksprese olan 80-kDa'lık protein kodlar. Gereç ve Yöntemler: MD hastalığına sahip farklı ailelerden 17 hastanın öncelikle elektromiyografilerinde (EMG) miyotonik deşarj saptanan hastalar bölümümüze refere edildi, daha sonra pedigri analizleri yapılan hastalara, moleküler analiziyle kesin tanı koyuldu. Genotip-fenotip ilişkisi için DMPK genindeki CTG tekrar sayılarıyla hastaların cinsiyeti, hastalığın başlangıç yaşı, tanı koyulma yaşı, hastalığın klinik şiddeti, soy geçmiş özellikleri, öz geçmişlerinde cerrahi operasyon geçirip geçirmedikleri ve ailede başka etkilenen birey varlığı araştırıldı. Bulgular: Afyonkarahisar'ın farklı bölgelerinden, aralarında akrabalık bulunmayan 17 farklı hastanın DMPK genindeki CTG tekrar sayılarında artış ve bazı hastalarda geniş ailesel etkilenim tespit edildi. Sonuç: MD hastalığında, CTG tekrar sayısı artışıyla hastalığın başlama yaşı arasında ters orantı olmasına karşın, klinik bulgularla CTG tekrar sayısı arasında ilişki yoktur. Güç kaybı ve kaslarda gevşeme kusuruyla ortaya çıkan MD açısından en önemli bulduğumuz, hastamız klinik olarak EMG'de miyotonik deşarjlara sahip olup MD tanısı alan, ancak tekrar sayısı açısından incelendiğinde DMKP1 geninin her 2 alleli için 8/17 sonucuyla genetik açıdan hastamızın normal tekrar sayısına sahip olmasıdır. Antisipasyon ve değişken ekspresyon sık gözlendiği için hastaların mutlaka genel ve detaylı olarak genetik, klinik, radyolojik ve laboratuvar olarak değerlendirilmesi gerekir.

Anahtar Kelimeler: Miyotonik distrofi hastalığı; üçlü tekrar artışı; DMPK geni
ABSTRACT
 Objective: Myotonic dystrophy disease (MD) is a progressive neurodegenerative disease with an autosomal dominant genetic inheritance, with increased CTG repeat sequences. Myotonic dystrophy protein kinase or dystrophy myotonica protein kinase (DMPK) gene (Chr19: 45,769,717-45,782,552-ENSG00000104936), also known as myotonine-protein kinase, located on the long arm of chromosome 19, codes for an 80-kDa protein expressed in skeletal and cardiac muscle. Material and Methods: 17 patients from different families with myotonic dystrophy disease were first referred to our department with myotonic discharge in their electromyography (EMG), pedigree analyzes and diagnosed with molecular analysis. For genotype-phenotype relationship; of CTG repeats in the DMPK gene, sex, the age of onset of the disease, the age of diagnosis, the clinical severity of the disease, family history characteristics, and the presence of other affected individuals in the family were investigated. Results: An increase in the number of CTG repeats in the DMPK gene of 17 different patients from different regions of Afyonkarahisar, among whom there is no consanguinity, and a wide familial influence in some patients were detected. Conclusion: Our patient, whom we find most important in terms of Myotonic Dystrophy, our patient clinically has myotonic discharges in EMG and is diagnosed with myotonic dystrophy, but has a genetically normal number of repeats with a result of 8/17 for both alleles of the DMKP1 gene when examined in terms of the number of repeats. Since antisipation and variable expressivity are frequently observed, patients should be evaluated in general and detailed genetic, clinical, radiological and laboratory.

Keywords: Myotonic dystrophy disease; triple repeat increases; DMPK gene
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