Analysis and evaluation of correlation between DNA polymorphism in the genes MTHFR, PAI-1 and serum creatinine, creatinine clearance and albumin/creatinine ratio in morning urine of patients with type 2 diabetes mellitus and diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy is a major microangiopathic complication of type 2 diabetes and a leading cause of chronic kidney disease (CKD).

Clinical characteristics, disease evolution and survival in patients with chronic myeloid leukemia, BCR-ABL1 (+) and T315I mutation.

INTRODUCTION: The T315I mutation in patients with chronic myeloid leukemia (CML) has been associated with therapeutic resistance and an unfavourable prognosis. AIM: To study the frequency of T315I mutation in patients with CML, BCR-ABL (+), their clinical characteristics, disease evolution, and median survival. PATIENTS AND METHODS: We studied 75 patients with CML and BCR-ABL1 (+). T315I mutation was detected by digital droplet PCR and BCR-ABL1 was analyzed by RT-PCR. A comparative analysis was performed by sex, age, disease phase, risk group, treatment, molecular response (MR), and median survival in T315I (+) and T315I (-) patients. RESULTS: T315I mutation was detected in 11 patients (14.7%). No significant difference was found in the phase, risk group, and first-line therapy. A significantly higher proportion of T315I (+) did not achieve MR >3.5 log: 8 (72.7%) vs. 22 (34.4%) (p=0.023). The lowest mean BCR-ABL1 levels were significantly higher in the CML T315I (+) group compared to the CML T315I (-) group: 12.1±6.0 vs. 3.77±1.28 (p=0.009). The median survival of T315I (+) patients was significantly shorter: 73 months vs. 175 months (p<0.0001, CI 95%). CONCLUSIONS: Our data confirm the world experience on the frequency of T315I mutation, including the unfavourable evolution, resistance to TKI treatment and short survival. ddPCR is a highly sensitive method for early detection of genetic mutations which gives the chance for effective treatment.

Clinical and molecular-cytogenetic studies of cryptic chromosome aberrations in individuals with idiopathic mental retardation and multiple congenital malformations.

UNLABELLED: Cryptic chromosome aberrations are a common cause of idiopathic mental retardation and multiple congenital malformations syndromes (MR/MCM). MATERIAL AND METHODS: This study describes results and compares three methods for detection of submicroscopic chromosome aberrations in 76 children with MR/MCM and normal routine G-banded karyotype. RESULTS: Cryptic chromosome aberrations were detected in 15 patients (19.7%): in 3 of 19 patients (15.8%) by subtelomeric fluorescent in situ hybridization (FISH), in 5 of 47 patients (10.6%) by Multiplex Ligation Dependent Probe Amplification (MLPA) and in 7 of 23 patients (30.4%) by array-Comparative Genome Hybridization (array-CGH). Seven deletions, four duplications and four complex rearrangements have been diagnosed in the present study. Six were de novo and 2 were inherited from a parent carrier of balanced translocation. DISCUSSION: We observed a slightly higher imbalance incidence compared to the literature. Among these aberrations there were well known syndromes as well as some rare variants. CONCLUSION: This study confirms the utility of molecular-cytogenetic screening in patients with MR/MCM. We suggest array-CGH as the most reliable technique with a high diagnostic yield.