A Filipino child with schinzel-giedion syndrome

@#Schinzel-Giedion syndrome is a rare condition characterized by dysmorphic features, neurologic features, urogenital abnormalities, and radiographic changes. The etiology has been traced to mutations in the SETBP1 gene. We report a Filipino patient with features suggestive of Schinzel-Giedion Syndrome and the first to be confirmed through molecular testing.

Clinical significance of SETBP1 gene mutation in patients with myelodysplastic syndrome / 肿瘤

Objective: To investigate the mutation frequency of SET binding protein 1 (SETBP1) gene in patients with myelodysplastic syndromes (MDS), and the clinical characteristics and prognosis of patients with SETBP1 gene mutation. Methods: From January 2008 to August 2017, all of 201 patients with primary MDS were recruited in this study. The conventional karyotype analysis was carried out by R banding technique. Genomic DNA was extracted from mononuclear cells in bone marrow, and was amplified through allele-specific PCR. The sequences of SETBP1, additional sex combs like 1(ASXL1), calcineurin B-like protein (CBL), myeloproliferative leukemia protein (MPL), Janus kinase 2 (JAK2) and tumor suppressor 53 (TP53) genes were detected by DNA sequencing directly. The clinical and laboratory features of 201 patients with primary MDS were analyzed. Results: Among 201 MDS patients, SETBP1 gene mutation was found in 25 patients, with a mutation rate of 12.4%. The mutation rate of SETBP1 gene in MDS patients with multilineage dysplasia was higher than that in WHO subtypes of MDS patients. Compared with the wild type of MDS patients, the patients with SETBP1 gene mutation had higher count of leukocyte, lower trend of the platelet and hemoglobin. In the cytogeneticaspect, the patients with SETBP1 gene mutation were often associated with chromosomal abnormalities such as -7/del (7q) or i (17) (q10), accompanied with ASXL1 gene mutation (both P < 0.001), and more prone to transfer to leukemia. Compared with the wild type of MDS patients, the patients with SETBP1 gene mutation had shorter median survival time and the lower trend of the median progression-free survival, suggesting they had a poor prognosis. Conclusion: SETBP1 gene mutation is an important molecular marker of MDS, and the patients with SETBP1 gene mutation have a poor prognosis.

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

BACKGROUND: Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. METHODS: Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. RESULTS: Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. CONCLUSIONS: Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.

Correlation of Genomic Characteristic with Disease Progression in Polycythemia Vera / 天津医药

Objective To screen mutations in genes including ASXL1, TET2, IDH1, IDH2, SETBP1, MPL515, JAK2 exon 12 and JAK2V617 in 135 polycythemia vera (PV) patients. To assess progreasson and genomics characteristics post polycythemic myelofibrosis. Methods DNA sequencing of ASXL1(Exon12),TET2 (Exons 3-11),IDH1(Exon4),IDH2(Ex-on4),SEPBP1(Exon4),JAK2 exon 12 and MPL515 (Exon 10) genes were carried out using Sanger method. JAK2V617 muta-tion was detected by allele-specific PCR in patients with PV. In the mean time, the mutation load of JAK2V617F allele (V617F%) was evaluated by real-time PCR using Tagman MGB probe. Then, the significant of gene mutations and clinical outcomes of post-PV Myelofibrosis(PPMF)was analyzed. To study risk factors of PPMF, logistic regression were employed. Results ASXL1, TET2, IDH1, IDH2 were mutated in 7.69%(8/104), 5.26%(1/19) , 0.08%(1/120) and 0.08%(1/121) of all PV patient respectively. JAK2 was mutated in 82.22%(111/135) of PV patients with mutation rate of exon12 of 2.96%(4/135) and there were no mutation of MPL515 and SETBP1 in PV patients. ASXL1 mutation was found in 31.82%(7/22) PPMF patients. Spearman analysis showed that ASXL1 is correlated with JAK2V617F (V617F%) (rs=0.298,P=0.002). The hemo-globin was lower in patients with ASXL1 mutation than patient without mutation (wild type). Leukocyte count, V617F%>50%rate, thrombosis and PPMF were higher in patients with ASXL1 mutation than that of ASXL1 wild type(P＜0.05). ASXL1 mu-tation, V617F%>50% rate and splenomegaly were all risk factors of PPMF. Conclusion ASXL1 mutation is the risk-fac-tor of PPMF and may promote V617F%by some mechanism.