Turkiye Klinikleri Journal of Internal Medicine

.: ORIGINAL RESEARCH
Huntington Hastalığına Sahip Hastaların CAG Tekrar Sayıları ile Genotip ve Klinik Bulguların Değerlendirilmesi: Tek Merkez Deneyimi
Evaluation of Genotype and Clinical Findings with CAG Repeat Numbers of Patients with Huntington's Disease: Single Center Experience
Muhsin ELMASa, Serap TUTGUN ONRATa, 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 Intern Med. 2020;5(3):112-9
doi: 10.5336/intermed.2020-74379
Article Language: TR
Full Text
ÖZET
 Amaç: Huntington hastalığı (HH), otozomal dominant genetik geçiş özelliği gösteren, motor, psikiyatrik ve bilişsel içerikli klinik bulgularla karakterize, ilerleyici nörodejeneratif bir hastalıktır. Kromozom 4'ün kısa kolunda lokalize HTT(IT15) GRCh38; Chr4: 3,041,422-3,243,960-ENSG00000197386 geni, huntingtin proteinini kodlar. HH'de, bu gende normalden fazla (normal 9-35) sitozin, adenin, guanin (CAG) tekrar dizisi artışı söz konusudur. Gereç ve Yöntemler: HH'ye sahip 6 farklı aileden 6 hastanın, öncelikle moleküler analiz (üçlü tekrarlı primed polimeraz zincir reaksiyonu) ile kesin tanısı koyuldu. Sonrasında, bu 6 hastanın HTT(IT15) genindeki CAG tekrar sayıları ile hastaların cinsiyeti, hastalığın başlangıç yaşı, tanı koyulma yaşı, hastalığın klinik şiddeti, istemsiz koreik hareket varlığı, duygu-durum ve mental etkilenim varlığı, soy geçmiş özellikleri, öz geçmişlerinde cerrahi operasyon geçirip geçirmedikleri ve nöbet öyküleri araştırıldı. Ayrıca hastaların, detaylı pedigri analizi yapıldı ve hastalığın kalıtım kalıbı, ailede başka etkilenen birey varlığı araştırıldı. Böylece hastalığın penetransı ve genotip-fenotip ilişkisi yorumlandı. Bulgular: Afyonkarahisar'ın farklı bölgelerinden, aralarında akrabalık bulunmayan 6 farklı hastanın HTT(IT15) genindeki CAG tekrar sayıları sırasıyla 45, 37, 40, 37, 40, 47 olarak saptandı. Hastalığın başlangıç yaşları sırasıyla 37, 48, 65, 54, 62, 36 olarak tespit edildi. Tüm hastaların pedigri analizleri yapıldı. Sonuç: HH'de, CAG tekrar sayısı artışı ile hastalığın başlama yaşı arasında ters orantı olmasına karşın çalışmamızda, klinik bulgularla CAG tekrar sayısı arasında ilişki yoktur. Koreik hareketler, demansa kadar varan kognitif bozukluklar, psikiyatrik bulgular, klinik tablonun temel özellikleridir. HH, antisipasyon ve klinik değişkenlik gösterdiği (variable expressivite) görülen bir hastalıktır. Çalışmamızda da bazı hastalarda antisipasyon, bazı hastalarda değişken ekspresyon gözlenmiştir. Antisipasyon ve değişken ekspresivite sık gözlendiği için hastaların mutlaka genel ve detaylı olarak genetik, klinik, radyolojik ve laboratuvar olarak değerlendirilmesi gerekir.

Anahtar Kelimeler: Huntington hastalığı; korea; üçlü tekrar artışı; antisipasyon; değişken ekspresivite; TP-PCR
ABSTRACT
 Objective: Huntington disease (HD) is a progressive neurodegenerative disease which has autosomal recessive inheritance and characterized by motor, psychiatric and cognitive clinical findings. The responsible gene is called HTT(IT15) GRCh38; Chr4: 3,041,422-3,243,960-ENSG00000197386, localized at the short arm of the chromosome 4 and codes the huntingtin protein. In HD, there are more cytosine, adenine, guanine (CAG) repeats than normal in this gene. Material and Methods: Firstly, 6 patients from 6 families that have HD were diagnosed by molecular analysis. Then, we investigated the CAG repeat numbers in the patients' HTT(IT15) genes, their genders, age of onset, age of diagnosis, clinical severity of the disease, presence of involuntary choreic movements, presence of affective and mental changes, family history, surgery and seizure history. Also the patients' detailed pedigree analysis was made. The inheritance pattern of the disease and presence of any other affected family member were investigated. Results: The CAG repeat numbers in HTT(IT15) genes of 6 different unrelated patients from different regions of Afyonkarahisar were detected as 45, 37, 40, 37, 40, 47. The age of onset of the disease was determined as 37, 48, 65, 54, 62, 36, respectively. All patients' pedigree analysis was made and in some patients' families broad affection was detected. Conclusion: Although there is an inverse proportion between CAG repeat number and age of onset in HD, there isn't a correlation between between clinical findings and CAG repeat number. Chore movements, cognitive disorders up to dementia, psychiatric symptoms are the main features of the clinical picture. HH is a disease seen with anticipation and clinical variable expressivity. In our study, anticipation was observed in some patients and variable expression was observed in some patients. Since anticipation and variable expressivity are frequently observed, patients should be evaluated in general and detailed genetic, clinical, radiological and laboratory.

Keywords: Huntington disease; chorea; trinucleotide repeat expansion; anticipation; variable expressivity; TP-PCR
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