Allogeneic hematopoietic stem cell transplantation for Crohn disease complicated with myelodysplastic syndrome: A case report.

RATIONALE: Myelodysplastic syndrome (MDS) can be complicated with Crohn disease (CD). Irritable bowel disease (IBD) associated with MDS has already been reported in the past; however, hematopoietic stem cell transplantation (HSCT) is rarely performed. Herein, we report a case of CD with MDS for HSCT. PATIENT CONCERNS: A 41-year-old man was hospitalized due to abdominal pain and intermittent fever for 40 days. Two years later, he was readmitted due to abdominal pain and diarrhea with fever for 10 days. DIAGNOSIS: Symptoms, laboratory examinations, and imaging findings of the patient were indicative of CD complicated with MDS. INTERVENTIONS: An allogeneic HSCT was performed. OUTCOMES: He died of severe lung infection 125 days post-transplantation. LESSONS: The number of cases of CD combined with MDS remains insufficient, and no consensus opinions are available to date. Hence, HSCT is a very potential treatment method. Additional experiences are needed to determine its effectiveness.

Impact of Chemotherapy Delay on Overall Survival for AML with IDH1/2 Mutations: A Study in Adult Chinese Patients.

The effect of time from diagnosis to treatment (TDT) on overall survival of patients with acute myeloid leukemia (AML) remains obscure. Furthermore, whether chemotherapy delay impacts overall survival (OS) of patients with a special molecular subtype has not been investigated. Here, we enrolled 364 cases of AML to assess the effect of TDT on OS by fractional polynomial regression in the context of clinical parameters and genes of FLT3ITD, NPM1, CEBPA, DNMT3a, and IDH1/2 mutations. Results of the current study show IDH1/2 mutations are associated with older age, M0 morphology, an intermediate cytogenetic risk group, and NPM1 mutations. TDT associates with OS for AML patients in a nonlinear pattern with a J shape. Moreover, adverse effect of delayed treatment on OS was observed in patients with IDH1/2 mutations, but not in those with IDH1/2 wildtype. Therefore, initiating chemotherapy as soon as possible after diagnosis might be a potential strategy to improve OS in AML patients with IDH1/2 mutations.

High IDH1 expression is associated with a poor prognosis in cytogenetically normal acute myeloid leukemia.

The prognostic value of IDH1 mutations has been systematically evaluated in acute myeloid leukemia (AML) patients recently. However, the role of IDH1 expression in AML is still under exploration. To investigate the clinical significance, we analyzed the IDH1/2 expression in 320 patients with cytogenetically normal AML (CN-AML) by quantitative real-time reverse-transcription polymerase chain reaction. High expression of IDH1 was predominant in patients with FLT3-ITD and DNMT3A mutations and less prevalent in cases with CEBPA double allele mutations. Strong association was observed between high IDH1 expression and low expression of microRNA 181 family. Prognosis was adversely affected by high IDH1 expression, with shorter overall survival and event-free survival in the context of clinical characteristics, including age, WBC count, and gene mutations of NPM1, FLT3-ITD, CEBPA, IDH1, IDH2 and DNMT3A in CN-AML. Moreover, the clinical outcome of IDH1 expression in terms of overall survival, event-free survival and complete remission rate still remained in multivariate models in CN-AML. Importantly, the prognostic value was validated using the published microarray data from 79 adult patients treated according to the German AMLCG-1999 protocol. Our results demonstrated that high IDH1 expression is associated with a poor prognosis of CN-AML.

[The clinical manifestation and linkage analysis in one Chinese family with congenital fibrosis of extraocular muscles].

OBJECTIVE: To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscles and to identify the location of candidate gene of the disease in chromosome. METHODS: The clinical feature of all affected members in this family were examined. A genome-wide linkage screening was conducted. Direct genomic sequencing was used to evaluate the candidate gene KIf21A. RESULTS: Four affected members in the pedigree were born with classic phenotype of CFEOM. By linkage analysis the disease gene was mapped to chromosomal region 12p11.2-q12 defined by microsatellite markers D12S1648 and D12S1668. The maximum Lod Score was 2.12 (D12S1090). Direct sequence showed no mutation in all exons and exon-intron boundaries of the candidate gene KIF21A, a polymorphism substitution occurred in the exon 21. CONCLUSIONS: The disorder in this family should be referred as CFEOM1 which was inherited as an autosomal dominant trait. The candidate gene was linked to CFEOM1 locus on chromosome 12p11.2-q12, between marker D12S1648 and D12S1668. It's more likely that KIf21A is not the disease causing gene in this family.

[Novel splice-site mutation in the pre-mRNA splicing gene PRPF31 in a Chinese family with autosomal dominant retinitis pigmentosa].

OBJECTIVE: To identify mutations in a four-generation Chinese family with retinitis pigmentosa and to investigate its clinical phenotype. METHODS: Ophthalmic and electrophysiological examinations of patients with RP were performed. A genome-wide scan and linkage analysis were conducted in this family. Direct genomic sequencing was used to evaluate the candidate gene. A restriction assay was used to confirm the mutation status in this family, and to exclude it as a polymorphism in a reference population. RESULTS: The mutation gene was mapped close to RP11 in chromosomal region 19q13.4 by linkage analysis. A novel single heterozygous base substitution (G > C) was detected at the beginning of intron 8 in the PRPF31 gene whereby the consensus GT dinucleotide of the intron 8 splice donor site was changed to CT. The mutation was co-segregated completely with the disease phenotype, but was absent in the unaffected relatives and in 100 reference subjects, thus supporting its pathogenic nature in this family. The clinical findings of RP patients were consistent with a relatively severe and diffuse type of RP. CONCLUSION: A novel splice site mutation (IVS8 + 1G > C) in the PRPF31 gene caused retinitis pigmentosa in the four-generation Chinese RP family studied.