الفهرس 
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Abstract
Beta thalassemia is a genetic disorders characterized by deficiency in the synthesis of beta-globin chains of hemoglobin. Phenotypically, beta thalassemia is categorized into trait, transfusion dependent or no transfusion dependent thalassemia. TDT patients are at great risk for many medical complications and organ damage duo to long-term transfusion therapy, iron overload and medications.
In the heart, LV diastolic dysfunction, heart failure and arrhythmia due to either severe anemia or iron overload can occur. Cognitive impairment due to many factors such as anemia, repeated transfusions, visual and auditory toxicity of deferoxamine and increased iron levels had been reported frequently in those patients.
OPG/RANKL/RANK axis mediated inflammation was implicated in iron-mediated heart diseases, central nervous system functions and multiple disease’s mechanisms. They are involved in endothelial physiology and play an active role in pathological angiogenesis, cell survival and in vascular calcification
The aim of this study is to assess the relationship between the genetic variants, OPG, RANKL , RANK and cardiac abnormalities detected by cardiac magnetic resonance T2* examination and cognitive impairment using IQ tests in children with TDT.
This study included 60 TDT children and 60 normal controls. All were subjected to thorough history taking, complete medical examination and laboratory investigations (Genotyping (by PCR RFLP method) for: OPG, RANK, RANKL, cardiac MRI, Wechsler Intelligence Scale for Children, Third Edition).
Our results revealed that TDT children had significantly lower T2, EF, total, verbal, and performance IQ than controls.
Regarding cardiac iron over load related MRI findings in TDT children in relation to OPG-RANK-RANKL axis, OPG rs2073618 (G>C) genotype had significant effect on cardiac T2 * and TDT children with its GC polymorphism were significantly more frequent to have lower T2* than other polymorphisms . The A allele of RANKL rs2277438 (G>A) gene significantly had more frequent lower T2* . Only RANK rs75404003 (C> DEL) genotype had significant effect on cardiac dysfunction in TDT patients and children with its CC polymorphism had significant more frequent cardiac dysfunction than other polymorphisms while those with C DEL polymorphism and the DEL allele of that gene had signicantly more frequent normal ejection fraction .
On assessing IQ results in TDT children in relation to OPG-RANK-RANKL axis, RANK rs1805034 (C>T) polymorphisms had a significant effect on total IQ Children with its TT polymorphism had significantly lower total IQ than children with its CT polymorphism . Children having the CT polymorphism of rs9494782 (C>T) gene had significantly lower total IQ than children with the CC polymorphism. The G allele of the RANKL rs2277438 (G>A) had significantly lower total IQ with a significant unstandardized β coefficient . RANK rs1805034 (C>T) and RANKL rs2277438 (G>A) were significantly affecting verbal IQ with a significant unstandardized β coefficient of the latter. The homomutant TT genotype of RANK rs1805034 (C>T) had significantly lower verbal IQ than the CT heteromutant genotype . In contrast, the AA homomutant form of RANKL rs2277438 (G>A) had a significantly higher verbal IQ than the GG genotype . The GG genotype of RANKL rs2277438 (G>A) had a significantly lower performance IQ than the AA genotype. Furthermore, the G allele of the RANKL rs2277438 (G>A) had significantly lower performance IQ than the A allele with a significant unstandardized coefficient .
Wlile on assessing IQ results in controls in relation to OPG-RANK-RANKL axis, The GC genotype of OPG rs2073618 (G>C) had significantly lower total IQ than CC polymorphism ,CC polymorphism of RANK rs1805034 (C>T) had significantly lower total IQ than TT polymorphism with a significant unstandardized β coefficient and CC polymorphism of RANK rs75404603 (C> DEL) had significantly lower total IQ than C Del - with a significant unstandardized β coefficient .Furthermore, the C allele of had RANK rs1805034 (C>T) had significantly lower total IQ than the T allele with a significant unstandardized β coefficient and the C allele of the RANK rs75404603 (C> DEL) had significantly lower total IQ with a significant unstandardized β coefficient . RANK rs1805034 (C>T) polymorphisms was significantly affecting verbal IQ with a significant unstandardized β coefficient with its CC genotype had significantly lower verbal IQ than the TT genotype. Moreover, children with the C allele of that genotype had significantly lower verbal IQ with a significant unstandardized β coefficient . The GC genotype of OPG rs2073618 (G>C) had significantly lower performance IQ than the CC polymorphism. RANK rs75404603 (C> DEL) genotype in relation performance IQ had a significant unstandardized β coefficient. Children with the C allele of RANK rs1805034 (C>T) polymorphisms genotype had significantly lower performance IQwith a significant unstandardized β coefficient .
In conclusion, TDT patients had lower T2*, EF , total ,verbal and performance IQ. Some of the studied genes polymorphisms and alleles of OPG-RANK-RANKL axis had a significant effect on them.