بررسي هتروژنيتي باليني و شكست كروموزومي در بيمارانن ايراني مشكوك به آنمي فانكوني

Clinical heterogeneity and chromosome breakage in Iranian patients suspicious of Fanconi anemia

Background: Fanconi anemia (FA) is a rare autosomal recessi ve di sorder charac terized by short stature, ske le tal anomalies, increased incid ence of so lid tum ors and leuk emia, and bone marr ow fai lure (aplas tic anemia) . FA has been reported in all races and ethnic gro ups and affec ts men and women in an eq ual proporti on . The frequency of FA has been es timated at app roximat ely 1 per 360,000 live birth s. In some popul ations, including Ashken azi Jews, Turks, Sa udi Ar abians and Iran ians , this frequency appear s to be higher , probabl y as a result of the founder effec t and co nsa ng uineo us marr iage. Because of extensive ge net ic and clinica l he terogeneity (the age of onse t, clinica l manifestat ions and surviva l), diagn os is of FA on the basis of cl inic al da ta alone is unrel iable and its molecul ar dia gn osis is difficul t. The diagnosis of FA exploits the hyper sen sit ivity of FA lymphocytes and fibr obl asts to bifuncti onal alkylating age nts such as mitomycin C (MMC), diep oxybut an e (DEB) and nit rogen mustard and di fferent iates it fr om idiopathi c ap las tic anemia. In this study, in add ition to the patientsʹ clinica l pro files, a cy toge ne tic test usin g MMC was impleme nted for an accurate diagn osis of Fanco ni anemi a. Methods: In thi s study , the lymp hocytes of 20 pati ent s re ferred for FA, and those of their norm al sex-matche d controls, we re tre ated with three diffe rent co nce ntrat ions of mitomycin C (20, 30, 40 ng/ml) . Slides were prepared and solid sta ined. In order to determine the number and kind of chro mosome abno rma lities , 50 metaphase sprea ds from eac h culture were ana lyzed. Clinica l information was obtained from pat ient files . Results: Five pat ient s man ifes ted increased chromosome breakage with .MMC, conftnning the FA diagnosi s. Two di f ferent co nce ntra tions of MMC (30, 40 ng/rnl ) were mos t effective . Conclusion: Th e chro mosomal breakage test is important for the accura te diagnosis of Fanco ni anemia. DNA cross linki ng agents used to treat idiopa thic ap las tic anemia may be lethal for pati ents with FA. Thu s, ap las tic anemia pati en ts with unknown etio logy, in fant s with congen ital abnorma lities invo lved in FA and sib lings of FA pati ents should also be cytogenetically tested .