The Clinical Analysis On The Rare Intermediate Beta Thalassemia Genealogy

Objective:To explore the relationship between molecular basis and clinical phenotype by analyzing a rare intermediate beta thalassemia genealogy.Method:Collect the peripheral blood of the proband and its genealogy members,and perform the blood routine test and the hemoglobin analysis.Adopt single-tube multi-crack polymerase chain reaction?Gap-PCR?to detect common deletion-type?-thalassemia gene mutations,detect common non-deleted?-thalassemia gene mutations and point mutation?-thalassemia gene mutations by polymerase chain reaction?PCR?combined with reverse dot blot?RDB?.Detect rare deletion-type beta-thalassemia gene mutation using the Multiple Linkage Dependent Probe Amplification?MLPA?technique.Perform ultrasound,magnetic resonance T2-star?MRI T2*?examination of the heart,liver and spleen of the proband.Results:There were four members of the genealogy,individuals?-1,?-2 and?-2 showed no obvious anemia and jaundice,?-1?proband?had thalassemia characteristic——skull enlargement,a slight prominence of zygoma,eye distance slightly widened,nasal beam slightly flat,medium yellowish skin,slightly short,growth retardation.Ultrasonography of the liver and spleen showed that the anteroposterior diameter of the left liver was 81 mm,the length was 70 mm,the oblique diameter of the right liver was130 mm and liver is palpable at 4.7 cm below the right costal arch.The spleen was 70 mm thick.The right margin of the spleen was about 4 cm on the right side of the median line and 5 cm under the umbilical cord.Cardiac ultrasonography suggested complete endocardial pad defect,pulmonary hypertension,and MRI T2*examination revealed no iron deposits in the heart and severe iron deposition in the liver.The results of routine blood test and hemoglobin electrophoresis showed that mild microcytic hypochromic anemia existed in all the individuals,and the HbF of individuals?-1 and?-1increased significantly.There were no abnormalities in the detection of common?-thalassemia genes in the members of the genealogy.The results of common beta-thalassemia gene tests were as follows:?-1 genotype was:?^N/?^N,?-2genotype was:?^17M/?^N,?-1 genotype was:?^17M/?^17M,?-2 genotype was:?^17M/?^N.The MLPA test result confirmed the presence of a 27 kb deletion in the?-globin gene of?-1 and?-1,and the deletion range was:?-gene of the?-globin gene cluster and 3'-HS-1.Conclusion:?1?The proband presented with intermediate beta-thalassemia,the genotype is?^17M/?^SEA-HPFH.?2?In the detection of thalassemia,when the clinical phenotype is not consistent with the genotype,the possibility of rare gene mutation should be considered.Genealogy analysis and further testing of the probands and their genealogy should be carried out.?3??^17M/?^SEA-HPFH thalassemia is a rare type of thalassemia intermedia,which is easily missed and misdiagnosed clinically.MLPA detection is a reliable method for the diagnosis of?^17M/?^SEA-HPFH thalassemia in clinical work.