OBJECTIVE: To explore mutational characteristics of acute myeloid leukemia (AML) patients with CBFβ-MYH11⁺ and analyze the correlation between the mutations and partial clinical characteristics. METHODS: A total of 62 AML patients with CBFβ-MYH11⁺ were included and 51 candidate genes were screened for their mutations using targeted next-generation sequencing (NGS). The exon 12 of NPM1 , FLT3-ITD , and TAD, bZIP domains of CEBPA were detected by genomic DNA-PCR combined with sanger sequencing. RESULTS: Compared with RUNX1-RUNX1T1 ⁺ group, the patients with CBFβ-MYH11⁺ showed higher age, peripheral WBC level, initial induced complete remission (CR) rate, more commonly carried chromosomal abnormalities such as +22, and lower deletion ratio of sex chromosome (-X or -Y) (P<0.05). In AML patients with CBFβ-MYH11⁺, the most common mutation was NRAS , followed by KIT, KRAS , and FLT3-TKD . Compared with RUNX1-RUNX1T1⁺ group, NRAS and FLT3-TKD were more frequently mutated in patients with CBFβ-MYH11⁺ (51.6% vs 18.7%, 17.7% vs 3.8%) (P<0.05). CONCLUSION The genomic landscape and clinical characteristics of AML patients with CBFβ-MYH11⁺ are different from patients with RUNX1-RUNX1T1 ⁺.
Humans ; Genomics ; Leukemia, Myeloid, Acute/genetics* ; Myosin Heavy Chains

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.
Cardiac Myosins/genetics* ; Cardiomyopathy, Hypertrophic/genetics* ; Genotype ; Humans ; Mutation ; Myosin Heavy Chains/genetics* ; Pedigree ; Phenotype

OBJECTIVE: To identify the mutation type of non-muscle myosin heavy chain 9 (MYH9) gene and investigate the clinical features of a pedigree affected with MYH9 gene-related disease. METHODS: Peripheral blood samples of the proband and his family members were collected. Routine blood tests were performed, which included platelet counting and Wright's staining to observe the granulocyte inclusions and giant platelets. PCR was used to amplify exons 2, 17, 27, 31, 39 and 41 of the MYH9 gene, and the mutation site was determined by Sanger sequencing. RESULTS: All patients from the pedigree presented a typical triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. In addition, two patients had nephritis and cataract. All affected members carried a heterozygous missense mutation of c.5521G>A (p.glu1841Lys) in exon 39 of the MYH9 gene. The same mutation was not found among healthy members of the pedigree and the controls. CONCLUSION The c.5521G>A (p.Glu1841Lys) mutation in the MYH9 gene probably underlies the MYH9-related disease in this pedigree.
Female ; Genetic Testing ; Humans ; Male ; Molecular Motor Proteins ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Thrombocytopenia

OBJECTIVE: To analyze the prognostic factors of AML children with CBFβ/MYH11 positive. METHODS: Twenty-eight children with CBFβ/MYH11 positive treated in our hospital from May 2012 to June 2018 were selected, the clinical data and curative were analyzed and evaluated. RESULTS: Five-year OS and 5-year EFS rate of CBFβ/MYH11 positive AML children was 76.8% and 64.0% efficacy, respectively. Univariate analysis results showed that the OS rate of CBFβ/MYH11 positive AML children with WBC<60.0×10 CONCLUSION WBC level and XRCC-Thr241Met genotype at initial diagnosis are the major affecting factors for prognosis of AML children with CBFβ/MYH11 positive.
Child ; Chromosome Inversion ; Genotype ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Myosin Heavy Chains ; Oncogene Proteins, Fusion ; Prognosis

OBJECTIVETo explore the clinical features and mutations of MYO5B gene in a family affected with microvillus inclusion disease.

METHODSClinical data of an infant affected with microvillus inclusion disease was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. PCR amplification and Sanger sequencing were performed to analyze all the exons and their flanking sequences of the MYO5B gene.

RESULTSThe patient presented with complicated manifestations including respiratory distress syndrome, dehydration, acidosis, bowel dilatation, liver and kidney dysfunction, and severe and intractable diarrhea. A compound mutation of the MYO5B gene, i.e., IVS37-1G>C/c.2729_2731delC (p.R911Afs916X), was discovered in the patient. The former was a splice-site mutation inherited from the mother, while the latter was a frameshift mutation inherited from the father. Both were not reported previously.

CONCLUSIONBased on the clinical and molecular evidence, the patient was diagnosed with microvillus inclusion disease. Above finding has expanded the mutation spectrum of the MYO5B gene, which can provide valuable information for genetic counseling for the family.

Family ; Female ; Genetic Testing ; methods ; Genotype ; Humans ; Infant ; Malabsorption Syndromes ; genetics ; Male ; Microvilli ; genetics ; pathology ; Mucolipidoses ; genetics ; Mutation ; genetics ; Myosin Heavy Chains ; genetics ; Myosin Type V ; genetics ; Phenotype

Hypertrophic cardiomyopathy (HCM) is the most common monogenic inherited myocardial disease in children, and mutations in sarcomere genes (such as MYH7 and MYBPC3) are the most common genetic etiology of HCM, among which mutations in the MYH7 gene are the most common and account for 30%-50%. MYH7 gene mutations have the characteristics of being affected by environmental factors, coexisting with multiple genetic variations, and age-dependent penetrance, which leads to different or overlapping clinical phenotypes in children, including various cardiomyopathies and skeletal myopathies. At present, the pathogenesis, course, and prognosis of HCM caused by MYH7 gene mutations in children remain unclear. This article summarizes the possible pathogenesis, clinical phenotype, and treatment of HCM caused by MYH7 gene mutations, in order to facilitate the accurate prognostic evaluation and individualized management and treatment of the children with this disorder.
Child ; Humans ; Cardiomyopathy, Hypertrophic/therapy* ; Phenotype ; Troponin T/genetics* ; Mutation ; Carrier Proteins/genetics* ; Myosin Heavy Chains/genetics* ; Cardiac Myosins/genetics*

Microvillus inclusion disease (MVID) is an autosomal recessive disorder caused by biallelic mutations in the MYO5B or STX3 gene. Refractory diarrhea and malabsorption are the main clinical manifestations. The aim of this study was to investigate the clinical features and MYO5B gene mutations of an infant with MVID. A 21-day-old female infant was referred to the hospital with the complaint of diarrhea for 20 days. On physical examination, growth retardation of the body weight and length was found along with moderately jaundiced skin and sclera. Breath sounds were clear in the two lungs and the heart sounds were normal. The abdomen was distended and the veins in the abdominal wall were observed. The liver and spleen were not palpable. Biochemical analysis revealed raised serum total bile acids, bilirubin, transaminases and γ-glutamyl transpeptidase while decreased levels of serum sodium, chloride, phosphate and magnesium. Blood gas analysis indicated metabolic acidosis. The preliminary diagnosis was congenital diarrhea, and thus parenteral nutrition was given along with other symptomatic and supportive measures. However, diarrhea, metabolic acidosis and electrolyte disturbance were intractable, and the cholestatic indices, including transaminases, γ-glutamyl transpeptidase, bilirubin and total bile acids, remained at increased levels. One month later, the patient was discharged and then lost contact. On genetic analysis, the infant was proved to be a compound heterozygote of the c.310+2Tdup and c.1966C>T(p.R656C) variants of the gene MYO5B, with c.310+2Tdup being a novel splice-site mutation. MVID was thus definitely diagnosed.
Female ; Humans ; Infant, Newborn ; Malabsorption Syndromes ; diagnosis ; genetics ; Microvilli ; genetics ; pathology ; Mucolipidoses ; diagnosis ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Myosin Type V ; genetics

Adult ; Female ; Hearing Loss, Sensorineural ; Humans ; Male ; Molecular Motor Proteins ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Thrombocytopenia ; genetics

BACKGROUNDHypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the beta-myosin heavy chain (beta-MHC) are the most common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with HCM, and to analyze the correlation between the genotype and phenotype.

METHODSThe exons 3 to 26 of MYH7 were amplified by PCR, and the PCR products were sequenced in five non-kin HCM patients. A 17-year-old patient was detected to be an Arg723Gly mutation carrier. Then his family was gene-screened, and the correlation between genotype and phenotype was analyzed.

RESULTSThe mutation of Arg723Gly in a Chinese family with HCM was detected for the first time. With a C-G transversion in nucleotide 13,619 of the MYH7 gene, located at the essential light chain interacting region in S1, the replacement of arginine by glycine took place at amino acid residue 723. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atria enlargement. There was no obstruction in the left ventricular outflow tract. In his family, a total of 13 individuals were diagnosed HCM and 5 of them were dead of congestive heart failure at a mean age of 66-year-old. Eight living members were all detected to carry the mutation, in which 3 developed progressive heart failure. Moreover, the heart function of the people evidently deteriorates when their age are older than 50. The mutation and the disease show co-separated.

CONCLUSIONThe Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.

Adolescent ; Adult ; Cardiomyopathy, Hypertrophic, Familial ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation, Missense ; Myosin Heavy Chains ; genetics ; Ventricular Myosins ; genetics

OBJECTIVESTo identify the nonmuscle myosin heavy chain 9 (MYH9) gene mutation site in a May-Hegglin anomaly(MHA) patient, and to analyze the genotype of her relatives to exclude the inherit correlation between the proband and her family members.

METHODSInclusion bodies in neutrophils of the proband were examined by transmission electron microscope, and giant platelets by scanning electron microscope. The mutation "hot spot" on the MYH9 gene of the proband and her family members was amplified with polymerase chain reaction(PCR), and then sequenced in both directions to identify the mutant site.

RESULTS(1) The proband manifested with the typical MHA triad of giant platelet, thrombocytopenia and Dohle-like inclusion bodies in neutrophil. However, all of the proband's family members had no such anomaly. (2) Transmission electron microscope and scanning electron microscope confirmed that giant platelets and neutrophils inclusion bodies existed in the proband peripheral blood cells. (3) There was a missense mutation 5797 C-->T in the exon 40 of MYH9 gene which led to Arg changing into termination codon (Arg1933 stop). The proband also had a heterozygous mutation 4876A-->G in exon 33. There was no abnormal finding in the sites mentioned above in her mother, while her father carried the homozygous 4876A-->G mutation.

CONCLUSIONSThis MHA case is a sporadic one, in whose family a mode for autosomal dominant inheritance can not be established. The 5797C-->T substitution in MYH9 gene is a pathogenic mutation, however, 4876A-->G is simply a polymorphism.

Adult ; Female ; Hearing Loss, Sensorineural ; Humans ; Molecular Motor Proteins ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Polymorphism, Genetic ; Thrombocytopenia ; blood ; genetics