Ayça Törel ERGÜL, Suzan AKYILDIZ, Semra Baykal GÖKÇE

Osteogenezis İmperfekta Tip 4’lü Bir Olguda Heterozigot Vitamin D Reseptör Geni Polimorfizmi

Çalışmada dört yıl içerisinde hastanemizde doğan bebekler içinde immün olmayan hidrops fetalis tanısı alan olguların Osteogenezis imperfekta (OI) tip 4 otozomal dominant geçişli, tip1 kollajen genlerinde; kollajen tip I alfa 2 (COL1A2) ve çok daha nadir olarak kollajen tip I alfa 1 (COL1A1); nokta mutasyon veya küçük delesyonun saptandığı, kısayapı, osteoporoz ve /veya diffüz osteopeni ,tekrarlayan kırıklar ve normal skleranın gözlendiği ve diğer osteogenez imperfekta tipleri ile kıyaslığında çok daha nadir gözlenen klinik bir antitedir. Yazıda son 1 yıl içinde minör travmalarla 3 kez kırık oluşumu nedeniyle kliniğimize başvuran 15 yaşında erkek olgu sunulmuştur. Olgunun fizik muayenesinde vücut ağırlığı: 59 kg, boy: 150 cm, boy standart deviasyon skoru (boy SDS):-2.31, üst/ alt segment oranı:1.03 ve sklera rengi normaldi. Diğer sistem bulguları normaldi. Serum biyokimyası ve kalsiyum (Ca), fosfor (P), alkalen fosfataz (ALP), parathormon (PTH) normal aralıktaydı. 25(OH)D düzeyi 16.7 mcg /L ve 1,25-(OH)2D3 düzeyi (30 pg/ml) normaldi. Tekrarlayan kırık öyküsüne sahip olan olgumuzun lumbal kemik mineral dansitesi (BMD) osteoporoz ile uyumluydu (BMI z skoru: -3.1). Hastanın serumundan alınan DNA örnekleri amplifiye edildikten sonra revers hibridizasyon metodu kullanılarak yapılan moleküler analizinde COL1A1 heterozigotluğu ve Vitamin D reseptörü (VDR) gen polimorfizmi saptandı.Bu sonuçlar bu hastalıkta VDR anomalisinin de osteoporoza katkıda bulunduğunu düşündürmüştür. Diğer bir deyişle, VDR ve COL1A1 risk allallerinin saptanması osteoporozun herediter oluşunu belirlemede önem taşımaktadır.

Anahtar Kelimeler:

COL1A1, Osteogenesis imperfecta, Vitamin D reseptör gen polimorfi zmi

Heterozygous Vitamin D Receptor Gene Polymorphism in an Heterozygous Vitamin D Receptor Gene Polymorphism in an Osteogenesis Imperfecta Type IV Case

Osteogenesis imperfecta (OI) type IV is a clinical entity with autosomal dominant inheritance in type 1 collagen genes; collagen, type I, alpha 2 (COL1A2) and more rarely collagen, type I, alpha 1 (COL1A1) point mutation or small deletion, and short stature, osteoporosis and/or diffuse osteopenia, repeating fractures and observed as normal sclera and more rarely seen compared to other type of osteogenesis imperfecta. On the physical examination of a 15-year old male child admitted to our clinic three times last year with minor traumas and complaints of fractures, the weight was 59 kg, height 150 cm, height standard deviation score (height SDS) -2.31, and upper/lower segment ratio 1.03. The sclera color was normal and other physical examination fi ndings also normal. The serum alkaline phosphatase (ALP), calcium (Ca), phosphorus (P), parathormone (PTH) levels were within the normal range. The patient’s serum 25(OH)D level was 16.7 mcg/L but his 1.25-(OH)2D3 level (30 pg/ml) was normal. The lumbar bone mineral density (BMD) of our patient who had a repeating fracture history conformed with osteoporosis (BMI z score:-3.1). After amplifying the DNA samples obtained from the patient’s serum, the molecular analysis made by using the reverse hybridization method helped determine a heterozygous COL1A1 spl (s/s) and homozygous Vitamin D receptor (VDR) Bsml (B/B) gene polymorphism.This result brings to mind the contribution of the VDR anomalies in the development of the disorders accompanying hereditary osteoporosis. In other words, the determination of the risk alleles of VDR and COL1A1 together is important in identifying a hereditary component of osteoporosis

Keywords:

COL1A1, Osteogenezis imperfekta, Vitamin D receptor gene polymorphism,

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