ABSTRACT
BACKGROUND: The phenotypic severity of ß-thalassemia is highly modulated by three genetic modifiers: ß-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly in the HBB cluster, BCL11A (B-cell CLL/lymphoma 11A) and HBS1L-MYB (HBS1-like translational GTPase-MYB protooncogene, transcription factor) with regards to clinical severity. METHODS: A total of 149 patients were included in the study. HBA and HBB mutations were characterised using multiplex PCR, Sanger sequencing and multiplex ligationdependent probe amplification. In addition, 35 HbF polymorphisms were genotyped using mass spectrometry and PCR-restriction fragment length polymorphism (PCRRFLP). The genotype-phenotype association was analysed using SPSS version 22. RESULTS: Twenty-one HBB mutations were identified in the study population. Patients with HBB mutations had heterogeneous phenotypic severity due to the presence of other secondary modifiers. Co-inheritance of α-thalassemia (n = 12) alleviated disease severity of ß-thalassemia. In addition, three polymorphisms (HBS1LMYB, rs4895441 [P = 0.008, odds ratio (OR) = 0.38 (0.18, 0.78)], rs9376092 [P = 0.030, OR = 0.36 (0.14, 0.90)]; and olfactory receptor [OR51B2] rs6578605 [P = 0.018, OR = 0.52 (0.31, 0.89)]) were associated with phenotypic severity. Secondary analysis of the association between single-nucleotide polymorphisms with HbF levels revealed three nominally significant SNPs: rs6934903, rs9376095 and rs9494149 in HBS1L-MYB. CONCLUSION: This study revealed 3 types of HbF polymorphisms that play an important role in ameliorating disease severity of ß-thalassemia patients which may be useful as a predictive marker in clinical management.
Subject(s)
Fetal Hemoglobin/genetics , GTP-Binding Proteins/genetics , Multigene Family , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-myb/genetics , beta-Thalassemia/genetics , Adolescent , Adult , Child , Female , Humans , MaleABSTRACT
Spontaneous intracranial haemorrhage (ICH) is a rare complication of chronic immune thrombocytopenic purpura (ITP) in children. We report four patients with cITP who developed ICH. The latency between onset of ITP and ICH varied from 1-8 years. All our patients were profoundly thrombocytopenic (platelet count of <10 x 109/l) at the time of their intracranial bleed. The presenting features and management are discussed. All patients survived, three had complete neurological recovery while one had a minimal residual neurological deficit.
ABSTRACT
Invasive aspergillosis predominantly occurs in immunocompromised patients and is often resistant to different therapeutically strategies. However, mortality significantly increases if the central nervous system is affected. In this report we describe two cases of invasive aspergilosis, one with kidney involvement with a successful treatment while the other with pulmonary and cerebral involvement with a grave outcome.
