Objective To analysis the clinical manifestations of a large Spinocerebellar Ataxia 3 pedigree to pro-vide the information for the early diagnosis of Ataxia 3. Methods SCA3/ATXN3 gene was determined by using Poly-merase Chain Reaction and fragment analysis in the large pedigree members and patients ’clinical data was collected. Five patients underwent MRI imaging and fundus examination. Results There were eighteen clinical patients and twelve ATXN3 carriers in this Pedigree . In addition to ataxia, three patients presented with intellectual disability, one with cer-vical spondylosis, one with dysmyotonia, one with disorder in visual system, and seven with abnormality in autonomic ner-vous system. The MRI revealed that pons and cerebellar atrophy in some patients inordinately. Undus examination did not reveal any obvious abnormality. Conclusions The symptoms of SCA3 are heterogeneous in the same pedigree. When patients present with symptoms of cerebellar system, visual system and autonomic nervous system, or cervical spondylosis and intellectual disability, SCA3 should be considered.

BACKGROUND:Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE:To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS:Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION:Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.

BACKGROUND:Spinocerebel ar ataxia type 3 (SCA3) is a typical genetic neurodegenerative disease. To establish patient-specific disease models of genetic background contributes to studying the pathogenesis and exploring therapeutic manners.
OBJECTIVE:To observe the effectiveness of neural differentiation of induced pluripotent stem cel lines induced by SCA3 and the stability of CAG copy number.
METHODS:Skin tissue of SCA3 patient was obtained clinical y, and specific skin flbroblasts were isolated and cultured. Reprogramming fibroblasts could obtain induced pluripotent stem cel s. Patient-specific induced pluripotent stem cel s, normal person induced pluripotent stem cel s (NHF) and embryonic stem cel s (ES-10) were induced to differentiate. Flow cytometry was used to compare the efficiency of differentiation. Western blot assay was utilized to detect ataxin-3 protein expression in neurons. Polymerase chain reaction was applied to measure the CAG repeat number of SCA3/ATXN3 gene.
RESULTS AND CONCLUSION:Induced pluripotent stem cel s that had identical genetic background to fibroblasts were successful y obtained, and had similar morphology and multi-directional differentiation potential to human embryonic stem cel s. Each cel line could differentiate into neural stem cel s. The CAG number did not apparently alter before and after reprogramming as wel as induction of neuronal differentiation. The effectiveness of the differentiation of induced pluripotent stem cel s derived from SCA3 into neural stem cel s was lower than that of normal person-derived induced pluripotent stem cel s (NHF) and embryonic stem cel s (ES-10). These findings demonstrate that reprogramming can successful y establish human induced pluripotent stem cel s, and induced the differentiation of above cel s into neural stem cel s. In the whole process, CAG number did not obviously alter, which was consistent with body cel s of patients.

Since the first report of preimplantation genetic diagnosis success in clinical in 1989,it is technological development that has been the driving force of preimplantation genetic testing(PGT).As the early stage prenatal diagnosis, PGT is used in the setting of assisted reproduction to differentiate the genetically normal embryos from pathogenic mutations or chromosomal anomalies in order to increase the rates of fruitful pregnancy.PGT involves technologies of assisted reproduction, molecular detection and genetic counseling.The aim of this review is to, from the perspective of laboratory medicine, summarize the utilization and progress of molecular strategies in the field of PGT,and explore its future development.(Chin J Lab Med,2018,41:270-274)

OBJECTIVETo assess the value of array-based comparative genomic hybridization (array-CGH) for analyzing tissues derived from spontaneous abortion and stillbirth.

METHODSAgilent Human Genome CGH Microarray 4×44 K chip and Affymetrix Cytoscan 750 K Array were utilized to detect genome-wide copy number variations (CNV) in 43 fetuses with spontaneous abortion and stillbirth. All identified CNV were analyzed with references from Database of Genomic variants (DGV), database of DECIPHER, ISCA and OMIM, as well as comprehensive literature review to determine whether the identified CNVs were pathogenic. Parental DNA of two cases was also analyzed with the same arrays for pathogenic or unknown significant CNVs.

RESULTSAll of the 43 specimens were successfully analyzed. Clinically significant chromosomal aberrations were identified in 32 (74.4%) of the samples, which included 26 aneuploidies and 10 pathogenic CNV.

CONCLUSIONArray-CGH is a fast and effective method for analyzing tissues derived from spontaneous abortions and stillbirths which may be difficult to culture for karyotype analysis.

Abortion, Spontaneous ; diagnosis ; genetics ; Adult ; Chromosome Aberrations ; Comparative Genomic Hybridization ; methods ; DNA Copy Number Variations ; Female ; Fetus ; chemistry ; Humans ; Karyotyping ; Pregnancy ; Pregnancy Complications ; diagnosis ; genetics ; Stillbirth ; genetics ; Young Adult