Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Purpose: Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluati

Increased risk for acute lymphoblastic leukemia in children with cytochrome P450 A1(CYP1A1)- and NAD(P)H: quinone oxidoreductase 1 (NQO1)-inherited gene variants

Sem informação124, n.3, p. 2010318218

Lack of evidence for mutations or deletions in the CDKN2A/p16 and CDKN2B/p15 genes of Brazilian neuroblastoma patients

Neuroblastoma, the most common extracranial tumor in childhood, has a wide spectrum of clinical and biological features. The loss of heterozygosity within the 9p21 region has been reported as a prognostic factor. Two tumor suppressor genes located in this region, the CDKN2B/p15 and CDKN2A/p16 (cyclin-dependent kinase inhibitors 2B and 2A, respectively) genes, play a critical role in cell cycle progression and are considered to be targets for tumor inactivation. We analyzed CDKN2B/p15 and CDKN2A/p16 gene alterations in 11 patients, who ranged in age from 4 months to 13 years (male/female ratio was 1.2:1). The most frequent stage of the tumor was stage IV (50%), followed by stages II and III (20%) and stage I (10%). The samples were submitted to the multiplex PCR technique for homozygous deletion analysis and to single-strand conformation polymorphism and nucleotide sequencing for mutation analysis. All exons of both genes were analyzed, but no deletion was detected. One sample exhibited shift mobility specific for exon 2 in the CDKN2B/p15 gene, not confirmed by DNA sequencing. Homozygous deletions and mutations are not involved in the inactivation mechanism of the CDKN2B/p15 and CDKN2A/p16 genes in neuroblastoma; however, these two abnormalities do not exclude other inactivation pathways. Recent evidence has shown that the expression of these genes is altered in this disease. Therefore, other mechanisms of inactivation, such as methylation of promoter region and unproperly function of proteins, may be considered in order to estimate the real contribution of these genes to neuroblastoma genesis or disease progression

Mir-708-5p Is Differentially Expressed In Childhood Acute Lymphoblastic Leukemia But Not Strongly Associated To Clinical Features

[No abstract available]621177178Li, X., Li, D., Zhuang, Y., Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL (2013) Pediatr Blood Cancer, 60, pp. 2060-2067Scrideli, C.A., Assumpção, J.G., Ganazza, M.A., A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups (2009) Haematologica, 94, pp. 781-789Brandalise, S.R., Pinheiro, V.R., Aguiar, S.S., Benefits of the intermittent use of 6-mercaptopurine and methotrexate in maintenance treatment for low-risk acute lymphoblastic leukemia in children: Randomized trial from the Brazilian Childhood Cooperative Group-protocol ALL-99 (2010) J Clin Oncol, 28, pp. 1911-1918Oliveira, J.C., Scrideli, C.A., Brassesco, M.S., Differential miRNA expression in childhood acute lymphoblastic leukemia and association with clinical and biological features (2012) Leuk Res, 36, pp. 293-298Schotte, D., Chau, J.C., Sylvester, G., Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia (2009) Leukemia, 23, pp. 313-322Jiao, Y., Cui, L., Gao, C., CASP8AP2 is a promising prognostic indicator in pediatric acute lymphoblastic leukemia (2012) Leuk Res, 36, pp. 67-71Luo, X.Q., Ke, Z.Y., Huang, L.B., High-risk childhood acute lymphoblastic leukemia in China: Factors influencing the treatment and outcome (2009) Pediatr Blood Cancer, 52, pp. 191-19

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of £0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1