Onur ÖZER, Osman DEMİRHAN, Erdal TUNC, Hüseyin BAĞCI, Dilara KARAHAN, Nilgün TANRİVERDİ, Bertan YILMAZ, Ali İrfan GÜZEL, İbrahim KESER

Frajil X Sendromu Olduklarından Şüphelenilen Çocuklarda Sitogenetik ve Moleküler Araştırmalar

Amaç: Kalıtımla geçen mental retardasyonun en yaygın nedeni Frajil X sendromudur (FXS). X kromozomu üzerinde bulunan FMR1 geninde meydana gelen bir mutasyon, bu sendroma yol açmaktadır. Tanı için kromozom analizi ve moleküler genetik testlerden birine veya her ikisine birden başvurulabilmektedir. Bu çalışmada, hasta grubundaki (türk pediyatrik nöroloji hastalarında) FXS frekansı belirlenmeye çalışıldı. Yöntem: Bu çalışmada mental retardasyon, konuşma güçlüğü, hiperaktivite ve gelişme geriliği gibi şikayetleri bulunan veya frajil X fenotipi gösteren 107 hastada fragile X yaygınlığını belirlemek için sitogenetik ve moleküler taramalar yapıldı. 107 hastanın sadece 26’sı moleküler olarak değerlendirildi. Bulgular: Sitogenetik olarak incelenen 107 olgunun 8’inde frajil X pozitif hücrelere rastlandı. Buna göre erkek olguların % 4.7’sinde, kadın olguların ise % 2.8’inde frajil X pozitif hücrelere rastlandı. 14 olguda (%13.1) ise otozomal frajil bölgelere rastlandı. Bir olgunun 9. kromozomunda perisentrik inversiyona rastlandı. Moleküler analizi yapılan 26 olgunun tamamının CGG tekrar sayısı artışı bakımından normal oldukları tespit edildi. Sonuç: Frajil X sendromunun tanısında kromozom analizi ve moleküler yöntem birlikte kullanılmalıdır. Frajil X pozitif bireylerin bulunduğu ailelerin tüm bireylerinin hem sitogenetik ve hem de moleküler olarak taranmalarında fayda görülmektedir. Hastalara ve hasta ailelerine genetik danışmanlık verilmesinde yarar görülmektedir.

Anahtar Kelimeler:

Frajil X sendromu, FMR1 geni, sitogenetik ve moleküler taramalar

Cytogenetic and Molecular Investigation in Children with Possible Fragile X Syndrome

Objective: Fragile X syndrome (FXS) is the most common cause of inherited mental retardation and is due to a mutation in the X-linked FMR1 gene. Molecular genetic testing and chromosome analysis are indicated for this disorder. In this context, we tried to determine the frequency of the FXS, and other chro¬mosomal abnormalities of Turkish pediatric neurology outpatients. Materials and Methods: Cytogenetic and molecular screenings were performed to esti-mate the prevalence of the fragile X in 107 patients with mental retardation, language disorders, hyperactivity, develop¬mental delay or fragile X syndrome phenotype. Only 26 out of 107 patients were screened, molecularly. Results: Cytogenetically fragile X-positive cells was found in 8 cases (7.5%) of 107 patients; in 4.7% of males and in 2.8% of females. The autosomal fragile sites (FS) was found in 14 (13.1%) cases. One (0.9%) patient had pericentric inversion of chromosome 9. Molecular analysis were performed for 26 patients and all patients showed normal CGG expansion. Conclusion: In diagnosis of fragile X syndrome, chromosome analysis must be run in conjunction with the molecular studies. It is recommended that all members of the fragile X family under risk should be screened both by cytogenetic and molecular methods. Genetic counseling can be useful to patients and families considering genetic testing.

Keywords:

Fragile X syndrome, FMR1 gene, cytogenetic and molecular screenings,

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