Hatfieldvelasquez1924

Objective To explore the significance of chromosome 6 aberrations for the occurrence and prognosis of hematopathies. Methods Clinical data and the cytogenetic results of 99 patients with hematopathies and aberrations of chromosome 6 were analyzed. Results The patients mainly had acute lymphoblastic leukemia (ALL), lymphoma, multiple myeloma, and myelodysplastic syndrome. ALL was the most common among the selected disorders. Based on their main abnormalities, ALL patients were divided into +6/-6, 6p and 6q groups. No significant difference was found in the gender, hemoglobin and platelet count between the three groups (P> 0.05). The age and white cell count in those with 6q aberrations were significantly higher compared with the +6/-6 group (P less then 0.05). Multivariate COX analysis suggested that the 6p/6q aberrations and age are risk factors for the prognosis. The 1-year overall survival rate of the 6p and 6q groups were lower than that of the +6/-6 group (P less then 0.05). Conclusion Aberrations of chromosome 6 are common in B-cell disease, and patients with ALL and 6q aberration have a poorer prognosis. Analysis of chromosome 6 aberration has a significance for the prognosis.Objective To investigate the clinical and genetic features of a Chinese girl featuring mental retardation, intellectual disability, language development delay and epilepsy. Methods G-banded chromosomal karyotyping was carried out for the child. Genomic DNA of the patient and her parents was extracted and subjected to high-throughput sequencing. The results were analyzed with bioinformatic tools and validated by Sanger sequencing. Results The karyotype of the child was ascertained as 46,XX. Sequencing result showed that she has carried a de novo heterozygous c.1861C>T (p.R621X) variant of the SYNGAP1 gene. Conclusion The nonsense variant c.1861C>T (p.R621X) of the SYNGAP1 gene probably underlies the disease in this child. (1S,3R)-RSL3 clinical trial Above result has enabled genetic diagnosis and counseling for her family.Objective To explore the genetic basis for a patient with episodic ataxia and pyramidal tract signs. Methods The patient was subjected to high-throughput sequencing, Sanger sequencing and analysis of dynamic variant site associated with spinocerebellar ataxias (SCA). Results The patient was an adolescent male presenting with episodic ataxia, bilateral knee hyper-reflexia and ankle clonus. By genetic testing, he was found to harbor a c.1159-1162dupAAGT variant of PDHA1 gene. The same variant was not found in his parents and elder sister. No abnormalities were found by SCA dynamic variant screening. The patient was diagnosed as pyruvate dehydrogenase E1alpha deficiency due to variant of the PDHA1 gene. Conclusion The de novo c.1159-1162dupAAGT variant of the PDHA1 gene probably underlies the disease in the proband. Patients with pyruvate dehydrogenase E1alpha deficiency have complex phenotypes and very few have pyramidal tract involvement, which may be attributed to abnormal early neuronal development.Objective To explore the genetic basis for a child suspected for hypokalemic periodic paralysis. Methods Clinical data of the patient was collected, and venous blood samples were taken from the patient and his parents for the extraction of genomic DNA. Next generation sequencing (NGS) with target capture was carried out to detect potential variants. Suspected variants were validated by Sanger sequencing. Results The child developed fatigue without obvious reason at the age of 15. Laboratory test revealed hypokalemia but normal serum magnesium. Genetic testing discovered that he has carried two variants in the SLC12A3 gene, namely c.179C>T and c.539C>A. The patient was diagnosed with Gitelman syndrome. Conclusion For children with hypokalemia, genetic testing should be considered for the differential diagnosis of Gitelman syndrome from hypokalemia due to other causes.Objective To explore the genetic basis for a child with dihydropyrimidase (DHP) deficiency. Methods High-throughput sequencing was carried out for the child. Suspected variants were verified by using Sanger sequencing. Results The proband was found to carry compound heterozygous variants of the DPYS gene, namely c.1468C>T (a missense variant) and c.1339-1363del (a frameshifting variant). Conclusion The compound heterozygous variants of the DPYS gene probably underlie the DHP in this child. Above result has enabled genetic counseling and prenatal diagnosis for his parents.Objective To assess the value of next generation sequencing (NGS) for the prevention and control of thalassemia. Methods NGS was used to sequence 3083 clinical blood samples suspected for thalassemia during initial screening. Retrospective analysis was conducted on blood samples detected with rare genotypes of thalassemia and abnormal hemoglobin. Results NGS analysis of the 3083 samples has found 1089 subjects with thalassemia genotypes (alpha-thelassemia genotype 26.01%, beta-thalassemia genotype 6.71%, and alpha-compound-beta genotype 2.59%), which yielded a positive detection rate of 35.32%. Rare alpha-thalassemia genotypes including HBA2 c.123delG, HBA1 c.354_355insATC and Fusion gene, and rare beta-thalassemia genotypes including HBB c.-100G>A and HBB c.316-90A>G, were discovered. In addition, 19 patients were found to have abnormal hemoglobin, mainly including Hb Hamilton, Hb Hekinan II, Hb Shizuoka, Hb Owari, Hb New York, Hb J-Bangkok and Hb Port Phillip. Conclusion NGS can play a crucial role for improving of the prevention and control of thalassemia and formulating a screening system with better efficacy.Objective To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS). Methods The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis. Results A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function.