Mutlu KARKUCAK, Demet HAFIZOĞLU, Şebnem ÖZEMRİ SAĞ, Sevgen TANIR BAŞARANOĞLU, Orhan GÖRÜKMEZ, Şebnem SARA KILIÇ, Tuna GÜLTEN, Tahsin YAKUT, Yalçın KİMYA, Davut GÜL

TNFRSF11A RANK Gen Mutasyonu Saptanan Bir Ailede Prenatal Tanı: Bir Olgu Sunumu

Otozomal resesif osteopetrozis ORO genellikle infant veya çocukluk çağında ölüme yol açan ciddi bir hastalıktır. TNFSF11 geni tarafından kodlanan RANKL ve TNFRSF11A geni tarafından kodlanan RANK proteinleri osteoklast olgunlaşması için önemli olup bu genlerdeki mutasyonların ORO gelişiminde rol oynadığı gösterilmiştir. Bu yazıda aralarında akrabalık bulunan eşlerin 2 çocuğunda da TNFRSF11A geninde c.508 A→G homozigot mutasyonu pArg170Gly saptanmış. Bir sonraki gebelik sırasında CVS materyali üzerinde yapılan mutasyon analizinde, fetusta heterozigot mutasyon saptandı. Gebelik terme kadar devam etti ve sağlıklı bir erkek çocuk doğdu. Prenatal mutasyon analizi, mutasyonu bilinen hastalıklarda ebeveynin anksiyetesini rahatlatmak ve aileye genetik danışma vermek için önemlidir

Anahtar Kelimeler:

Mutasyon, TNFRSF11A geni, prenatal tanı

Prenatal Diagnosis in a Family of TNFRSF11A RANK Gene Mutation Detection: A Case Report

Autosomal recessive osteoporosis ARO is a severe disease causing death usually at infancy or childhood. RANKL coded by TNFSF11 gene and RANK coded by TNFRSF11A gene are important proteins for osteoclast maturation and it is indicated that mutation on these genes plays an important role for ARO development. It is reported in this article that c.508 A→G homozygote mutation pArg170Gly is observed in TNFRSF11A gene of 2 children of consanguineous couple. Mutation analysis performed on CVS material during the next pregnancy revealed heterozygous mutation in the fetus. The pregnancy was continued to term and a healthy boy was delivered. Prenatal mutation analysis is important for diseases with known mutations to relieve parental anxiety and provide genetic counselling for the family

Keywords:

Mutation, TNFRSF11A gene, prenatal diagnosis,

PDF

___

1. Gerritsen EJ, Vossen JM, van Loo IH, Hermans J, Helfrich MH, Griscelli C, Fischer A. Autosomal recessive osteopetrosis: variability of findings at diagnosis and during the natural course. Pediatrics 1994;93:247-53.
2. Abdel-Al YK, Shabani IS, Lubani MM, al-Ghawabi MA, Ibrahim MD, al-Mohtaseb S, et al. Autosomal recessive osteopetrosis in Arab children. Ann Trop Paediatr 1994;14:59-64.
3. Steward CG, Pellier I, Mahajan A, Ashworth MT, Stuart AG, Fasth A, et al. Working Party on Inborn Errors of the European Blood and Marrow Transplantation Group. Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis. Br J Haematol 2004;124:63- 71.
4. Phadke SR, Fischer B, Gupta N, Ranganath P, Kabra M, Kornak U. Novel mutations in Indian patients with autosomal recessive infantile malignant osteopetrosis. Indian J Med Res. 2010;131:508-14.
5. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med 2004;351:2839-49.
6. Villa A, Guerrini MM, Cassani B, Pangrazio A, Sobacchi C. Infantile malignant, autosomal recessive osteopetrosis: the rich and the poor. Calcif Tissue Int 2009;84:1-12.
7. Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS, Pangrazio A, et al. Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations. Am J Hum Genet 2008;83:64-76.
8. Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, et al. Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet 2007;39:960- 2.
9. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, et al. RANK is essential for osteoclast and lymph node development. Genes Dev 1999;13:2412-24.
10. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med 2004;351:2839-49.