Identification of gene mutation associated with familial dilated cardiomyopathy by whole-exome sequencing / 复旦学报（医学版）

Objective To identify the disease-causing gene in a Chinese pedigree with familial dilated cardiomyopathy (DCM) by whole-exome sequencing.Methods After collecting the clinical data and extracting the whole blood genomic DNA of the 5 family members form a Chinese DCM pedigree,whole-exome sequencing was performed to search the causative genes.Familial co-segregation analysis among the pedigree was subsequently confirmed by traditional Sanger sequencing.Results We performed whole exome sequencing (WES) on representative affected individuals and unaffected familial members from this pedigree.After comparison with variants identified in affected individuals and unaffected individuals,along with previously reported genetic mutations associated with DCM,we found that a heterozygous variant c.961 C＞T (p.Arg321Ter) in exon 6 of the LMNA gene in affected individuals matched the criteria to be the potential disease-causing gene,which was confirmed by Sanger sequencing.This stop-gain mutation leads to only a small part of LMNA-coding protein expressed,therefore we concluded that LMNA c.961 C＞T should be the causative mutation for this familial DCM case.Conclusions The nonsense mutation c.961 C＞ T in gene LMNA identified by whole-exome sequencing might be the pathogenic mutation in this DCM pedigree.

Clinical Characteristics and Therapeutic Efficacy Evaluation of 14 Cases of Solitary Myeloid Sarcoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, treatment and prognosis of solitary myeloid sarcoma (MS).</p><p><b>METHODS</b>The clinical data of 14 solitary MS patients were retrospectively analysed, including their clinical features and treatment, and were evaluated.</p><p><b>RESULTS</b>A total of 14 cases of solitary MS mainly occurred in middle-aged population with the median age 41 years old (17-62 years old). The involved sites were more extensive, including breast, testis, spinal canal, skin, gastrointestinal system, nose and so on. The poorly differentiated cells of small to medium size showed diffuse distribution, relatively consistent morphology and a higher ratio of cytoplasm. The nucleus is in round or oval shape with fine and dense chromatin. Pathological mitosis was easily observed. Expression of MPO, lysozyme, CD43, myeloid-derived cells were positive. Treatment methods included surgery, chemotherapy and stem cell transplantation. Median survival time of 14 patients was 22.5 months; overall survival (OS) was 35.7% (5/14), median disease-free survival reached to 10.4 months on averge (3.5 months to 16 months), and 2-year overall survival (OS) was 50.3%.</p><p><b>CONCLUSION</b>The incidence of solitary MS is low, with a tendency progressing to leukemia, the chemotherapy regimen of anthracycline+cytarabine combined with radiotherapy can achieve better clinical efficacy.</p>

Experimental study of SHP-1 promoter methylation in myelodysplastic syndromes and its related mechanism / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of SHP-1 promoter methylation on the pathogenesis and progression in myelodysplastic syndromes (MDS) and its related mechanism.</p><p><b>METHODS</b>63 MDS patients were divided into low-grade (LG) group and high-grade (HG) group according to IPSS score system. Bone marrow samples were collected. Methylation specific-PCR (MSP) were used to detect the status of SHP-1 promoter methylation in bone marrow (BM) samples from different risk MDS patients and MDS cell line, SKK-1. Western blot was used to detect signal transduction and activator of transcription (STAT3) activation in SKK-1 cell line and MDS patients.</p><p><b>RESULTS</b>No SHP-1 promoter methylation could be detected in healthy controls BM. Partially methylation was found in SKK-1 cell line. Methylation rate of SHP-1 gene promoter was found in BM of 24.2% of low-grade MDS patients and 63.3% of high-grade MDS patients, the difference between these two groups was statistically significant (P < 0.05); Patients were divided into different groups according to WHO subtype, chromosomal karyotype and blast cells in bone marrow, methylation rates of SHP-1 were significantly higher in RAEB-II, poor karyotype group and samples with 0.11-0.19 blast cells (P < 0.05); The phosphorylation protein of STAT3 was detected in SKK-1 cell line. The expression of phosphorylation STAT3 was significantly higher in HG group than in LG group (66.7% vs 18.2%) (P < 0.05). There was a significant correlation between SHP-1 promoter methylation and STAT3 phosphorylation.</p><p><b>CONCLUSION</b>Abnormal methylation of SHP-1 gene promoter might have tentative role in the pathogenesis and progression of MDS, which may be involved in STAT3 activation. Detection of SHP-1 promoter methylation may be helpful to evaluate the prognosis of MDS.</p>