Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings: a diagnostic conundrum / 소아과

Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

Aberrant myeloid antigen co-expression is correlated with high percentages of CD34-positive cells among blasts of acute lymphoblastic leukemia patients: an Indian tertiary care center perspective

BACKGROUND: Aberrant myeloid antigen (MA) co-expression and high expression of CD34 antigen on the blasts of acute lymphoblastic leukemia (ALL) patients are independently reported to have a role in pathogenesis and prognosis. This study was conducted to determine whether these two parameters are related. METHODS: A total of 204 cases of ALL were included in an analysis of blast immunophenotypic data. CD34 expression was categorized as low when less than 50% of blasts were CD34-positive (CD34low) and as high when 50% or more were CD34-positive (CD34high). RESULTS: Of 204 cases of ALL, 163 and 41 were of B-cell origin (B-ALL) and T-cell origin (T-ALL), respectively. Of all cases, 132 (64.7%) showed co-expression of MA and among these, 101 (76.51%) were CD34high, while the remaining 31 (23.48%) were CD34low. Of 72 cases without MA co-expression, 25 (34.72%) were CD34high and 47 (67.25%) were CD34low. Furthermore, of 163 cases of B-ALL, 111 showed co-expression of MA and 84 of these were CD34high. Of 52 cases of B-ALL without MA expression, 22 were CD34high. Among 41 cases of T-ALL, 21 co-expressed MA, 17 of which were CD34high. Moreover, all 20 cases of T-ALL without co-expression of MA were CD34low. These differences were statistically significant. CONCLUSION: We observed a strong correlation between aberrant MA expression and CD34high expression on the blasts of ALL. We hypothesize that these different patient subsets may represent unique prognostic characteristics.

Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients

BACKGROUND: Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. OBJECTIVE: The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. METHODS: Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. RESULTS: An increased frequency of the GSTT1 null genotype (p-value = 0.05) was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. CONCLUSION: GST deletions do not play a direct role in iron overload of sickle cell patients.

Genotypic influence of alpha-deletions on the phenotype of Indian sickle cell anemia patients

BACKGROUND: Some reports have shown that co-inheritance of alpha-thalassemia and sickle cell disease improves hematological parameters and results in a relatively mild clinical picture for patients; however, the exact molecular basis and clinical significance of the interaction between alpha-thalassemia and sickle cell disease in India has not yet been described. There is little agreement on the clinical effects of alpha-thalassemia on the phenotype of sickle cell disease. METHODS: Complete blood count and red cell indices were measured by an automated cell analyzer. Quantitative assessment of hemoglobin variants HbF, HbA, HbA2, and HbS was performed by high performance liquid chromatography (HPLC). DNA extraction was performed using the phenol-chloroform method, and molecular study for common alpha-deletions was done by gap-PCR. RESULTS: Out of 60 sickle cell anemia patients, the alpha-thalassemia genotype was found in 18 patients. Three patients had the triplicated alpha-genotype (Anti alpha-3.7 kb), and the remaining patients did not have alpha-deletions. This study indicates that patients with co-existing alpha-thalassemia and sickle cell disease had a mild phenotype, significantly improved hematological parameters, and fewer blood transfusions than the patients with sickle cell anemia without co-existing alpha-deletions. CONCLUSION: Co-existence of alpha-thalassemia and sickle cell anemia has significant effects on the phenotype of Indian sickle cell patients.