ABSTRACT
<p><b>OBJECTIVE</b>To study the copy number variation (CNV) in a Chinese Han autistic spectrum disorder (ASD) pedigree.</p><p><b>METHODS</b>The pedigree involved six siblings, and three of them were autistic. B lymphocytes of the pedigree were immortalized with EBV and used as studying materials. Karyotyping and Affymatrix 500k SNP chip assay were performed to assess the genetic defects among the members of the pedigree.</p><p><b>RESULTS</b>Karyotyping indicated that the chromosomes were normal. However, the 15q11 locus was located as de novo CNV region in all autistic siblings of the pedigree. In this locus, the fragment in 19827281-19998230 illustrated "loss" of CNV, while other three fragments with 37 kb, 1316 kb and 37 kb indicated "gain" of CNV.</p><p><b>CONCLUSION</b>In this study, olfactory genes OR11K1P, OR4Q1P, OR4H6P, OR4M2, etc. in the sites with loss and gain of CNV may provide a new clue for genetic research of autism spectrum disorder.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Child Development Disorders, Pervasive , Genetics , China , Ethnology , DNA Copy Number Variations , Genetics , Ethnicity , Genetics , Pedigree , Polymorphism, Single NucleotideABSTRACT
Objective: PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hy-pothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods: To test our hypothesis, approaches of protein wal-king with a yeast two-hybrid system (Y2H), pulling down in yeasts, co-immunoprecipitation and immu-nofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results: Candidate proteins including MYL6, PECAM1, CSH1,RAB7, p57KIP2, ACTG1, RBMS1 and PSG4-1ike were identified with selection mediums and preceding methods. Conclusion: With these candidate protein molecules, some protein complexes associating with PCBP1 are proposed, which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.
ABSTRACT
Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods: The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally, 12 patients (7 males and 5 females with age ranging 22-62 years, mean 43 years) were treated by this operation from August 2006 to August 2008. Results: The cells of fetal cerebellum were expanded by 107folds in undifferentiated state in the culture. After the operation, no rejection was detected. Follow up, the effective rates were 58. 3% after 3 months, 75.0% after 6 months, and 66.7% for 12-24 months (mean 18 months). Conclusion: the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA, but the long term effectiveness need to be taken in consideration.
ABSTRACT
Objective: Batten disease (BD), the juvenile form of neuronal ceroid lipofuscinosis (NCLs), is pathological characterized by finding lysosomal storage of autofluorescent lipofuscins with unique ultrastructural profiles. The gene underlying BD is designated CLN3 and encodes a protein, Battenin, of unknown function that localizes in lysosomes and/or mitochondria. Previously, we hypothesized that Battenin associates with other membrane protein(s) to form a membrane complex. Dysfunction of this complex could result in the pathological changes of BD, and possibly in other NCLs. Two such membranous proteins, the slow and fast Battenin-interactive proteins (BIPs and BIPf) of unknown functions, have been identified. In this study, we have characterized the functional domains of Battenin that interact with both BIP proteins. Methods: Protein-protein interactions with a yeast two-hybrid system were employed. A "deletion assay" was employed to localize the interactive segment(s). Different lengths of cDNA sequences lacking exon 1-5 were used to express CLN3-encoded proteins lacking N-terminal segments in the yeast two-hybrid system. N-terminal exons of CLN3 were deleted with PCR-cloning strategies.Results: We eliminated the possibility of interacting domains from the exon 7-encoded region because both Battenin and mBattenin interact with the BIP proteins. We have shown that peptide sequences encoded by exons 2 and 4 of CLN3 gene include the functional domains by which Battenin interacts with the BIP proteins. Conclusion: Our studies provide evidence that the N-terminus of Battenin is the functional domain for these protein interactions.
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Objective:To investigate the efficiency of maternal serum triple screening for the genetic abnormality in second-trimester and the morbidity of adverse pregnancy outcome in false positive results of the test. Methods: A total of 4 680 pregnant women with singleton pregnancies assigned in Obs & Gyn Hospital, Fudan University, underwent triple screening test (alpha fetoprotein, AFP; human chorionic gonadotropin, HCG and unconjugated estriol, uE3) by fluorescence enzyme immunoassay between 2003 and 2005. The valid MoM (Multiples of Median) value of mid-trimester serum AFP, uE3, and hCG and risk assessments was provided by Beckman Coulter Co. When applied in the prenatal Down syndrome screening service. The study compares the incidence of chromosomal abnormalities with Down syndrome in screen positive women and compares to the MoM value established in the literature. The risks of having a fetus with congenital abnormalities or of developing obstetric complications in the screen positive women with their matched controls.Results:The MoM values for the triple tests of our study are similar to established values of literature. Only 51.01% women with pregnancies agree to receive screening. Amniocentesis utilization rate was 55.12% in the screen-positive pregnancies. The false positive rate was 6.89% and the median of maternal age of the women was 28.13 (range 19 to 49) years old. Chromosomal abnormalities were identified in 21 pregnancies, including 9 cases of trisomy 21.The detection rate was 77.77%. Pregnancies with positive screening results had a significantly higher risk of adverse outcomes than those with negative results (P< 0.05). Whereas there was no difference in the incidences of fetal congenital appearance or skeleton abnormality. Conclusion: Adjusting MoM values of local unaffected populations is limited to increasing the detection rate. Because chromosomal defects have variable exhibitions, amniocentesis utilization is still a choice for screen-positive pregnancies. Screen-positive pregnancies had increased risk of chromosomal abnormalities.
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Objective: To evaluate the frequency of MSI in epithelial ovarian tumors and its relationship with clinicopathologic features. Methods: Ninety fresh specimens of epithelial ovarian tumors, including 74 primary and 16 secondary tumors, were collected. Microsatellite analysis was carried out using 5 mono- and dinucleotide markers from the National Cancer Institute Consensus Panel by fluorescence-labeled polymerase chain reaction. Results: Of 90 epithelial ovarian tumors analyzed, 18 demonstrated a high level of microsatellite instability (MSI-H), 30 demonstrated a low level of microsatellite instability (MSI-L), and the remaining 42 exhibited microsatellite stability (MSS). Frequency of microsatellite instability (MSI) at loci BAT-25 was higher than that at any other loci. No correlation was found between MSI level and patient age, tumor type, tumor differentiation (P>0.05). But the microsatellite instability-high phenotype correlates with clinical stage.It tended to occur more frequently in early-stage tumors (P=0.03). Conclusion: The frequent MSI in epithelial ovarian tumors suggests that it is an early event to involve in the development of epithelial ovarian tumors.
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Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.
ABSTRACT
Dystonia is a syndrome which is characterized by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. According to genetic basis, dystonia is classified into 13 subtypes. We mainly discussed two subtypes, DYT1 and DYT5, in this review. Early-onset primary dystonia is caused by the mutation of DYT1 gene, which leads to TORSINA abnormal. GTP cyclohydrolase 1 (GTPCH1)-deficient DRD(DYT5) is caused by the mutations of GCH1 gene. By genetic testing, we can confirm clinical diagnosis of each subtype and develop prenatal diagnosis for it.
ABSTRACT
Autism is a neurodevelopmental disorder characterized by impairments in social skills, language, and behavior. It is now clear that autism is not a disease, but a syndrome characterized by phenotypic and genetic complexity. The etiology of autism is still poorly understood. Available evidence from a variety of sources strongly suggests that many genetic disorders are frequently associated with autism for their similar phenotypes. Based on this fact, this review begins by highlighting several principal genetic syndromes consistently associated with autism (fragile X, tuberous sclerosis, Angelman syndrome, Pader-Willi syndrome, Rett syndrome, Down syndrome and Turner syndrome). These genetic disorders include both chromosome disorders and single gene disorders. By comparing the similar phenotype, protein marker and candidate genes, we might make some breakthrough in the mechanism of autism and other genetic disorders.