Ayça ERGÜR TÖREL, Suzan AKYILDIZ, Semra GÖKÇE BAYKAL

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 olgularınOsteogenezis imperfekta (OI) tip 4 otozomal dominant geçişli, tip1 kollajen genlerinde; kollajen tip I alfa 2 (COL1A2) veçok daha nadir olarak kollajen tip I alfa 1 (COL1A1); nokta mutasyon veya küçük delesyonun saptandığı, kısayapı, osteo- poroz ve /veya diffüz osteopeni ,tekrarlayan kırıklar ve normal skleranın gözlendiği ve diğer osteogenez imperfekta tipleriile kıyaslığında çok daha nadir gözlenen klinik bir antitedir. Yazıda son 1 yıl içinde minör travmalarla 3 kez kırık oluşumunedeniyle kliniğimize başvuran 15 yaşında erkek olgu sunulmuştur. Olgunun ﬁ zik 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. Diğersistem 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 öyküsünesahip olan olgumuzun lumbal kemik mineral dansitesi (BMD) osteoporoz ile uyumluydu (BMI z skoru: -3.1). Hastanınserumundan alınan DNA örnekleri ampliﬁ ye edildikten sonra revers hibridizasyon metodu kullanılarak yapılan moleküleranalizinde COL1A1 heterozigotluğu ve Vitamin D reseptörü (VDR) gen polimorﬁ zmi 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.

Heterozygous Vitamin D Receptor Gene Polymorphism in an Osteogenesis Imperfecta Type 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 morerarely seen compared to other type of osteogenesis imperfecta. On the physical examination of a 15-year old malechild 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 scleracolor 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 patients serum 25(OH)D level was16.7 mcg/L but his 1.25-(OH)2D3 level (30 pg/ml) was normal. The lumbar bone mineral density (BMD) of our patientwho had a repeating fracture history conformed with osteoporosis (BMI z score:-3.1). After amplifying the DNA samplesobtained from the patients serum, the molecular analysis made by using the reverse hybridization method helpeddetermine 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 accompanyinghereditary osteoporosis. In other words, the determination of the risk alleles of VDR and COL1A1 together is importantin identifying a hereditary component of osteoporosis.

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