OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.
Adenosine Deaminase/genetics* ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/genetics* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To detect mutations of ADAR gene in two pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Potential mutations of the ADAR gene were analyzed by Sanger sequencing of the probands from both pedigrees. Suspected mutations were validated by Sanger sequencing of other patients from both pedigrees as well as unrelated healthy individuals. RESULTS: A heterozygous nonsense mutation c.1325C>G (p.Ser442Ter) and a novel nonsense mutation c.1498C>T (p.Gln500Ter) were respectively identified in the ADAR gene among all patients from the two pedigrees but not among 200 healthy individuals. CONCLUSION Mutations of the ADAR gene probably underlie the DSH in the two pedigrees. Above findings have enriched the spectrum of ADAR gene mutation.
Adenosine Deaminase ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders ; congenital ; genetics ; RNA-Binding Proteins

This study was purposed to investigate the expression of ADAR1 isoforms of P110 and P150 during the development of murine leukemia. A Notch1 over-expressing murine T cell acute lymphoblastic leukemia model was used to study the expression of ADAR1. BMMNC were isolated at different stages of disease and CD45.2(+)GFP(+) leukemia cells were sorted by flow cytometry at late stage. The expression of ADAR1 was detected by real time quantitative PCR. The results showed that mouse bone marrow cells from both leukemia and control groups expressed P110 and P150. Difference of P110 and P150 mRNA expression were observed during the development of leukemia. The expression of P110 dramatically increased and was significantly higher than that in control group. However, the expression level of P150 in leukemia group decreased stably and reached one-fourth of that in control group at 14 day. Furthermore, similar expression patterns could be detected in sorted CD45.2(+)GFP(+) leukemia cells. It is concluded that the mRNA expressions of P110 and P150 show diverse patterns in the development of leukemia, suggesting that RNA editing mediated by ADAR1 isoforms may play different roles in leukemia.
Adenosine Deaminase ; genetics ; Animals ; Gene Expression ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Protein Isoforms ; genetics ; RNA Editing ; RNA, Messenger ; genetics ; RNA-Binding Proteins

OBJECTIVETo investigate the effect of ADAR1 on the occurrence and development of mouse T cell acute lymphoblastic leukemia (T-ALL).

METHODSLck-Cre; ADAR1lox/lox mice were generated through interbreeding. The lineage-cells of Lck-Cre; ADAR1lox/lox mice and the control were enriched respectively by the means of MACS, and the lin- cells were transfected with retrovirus carrying MSCV-ICN1-IRES-GFP fusion gene. Then the transfection efficiency was detected by the means of FACS, and the same number of GFP+ cells were transplanted into lethally irradiated recipient mice to observe the survival of mice in 2 recipient group after transplantation.

RESULTST cell-specific knockout ADAR1 mice were generated, and Notch1-induced T-ALL mouse model was established successfully. The leukemia with T-ALL characteristics occured in the mice of control group, but did not in the ADAR1 kmockout mice after transplantation.

CONCLUSIONSADAR1 plays a key role in the incidence and development of Notch1-induced T-ALL.

Adenosine Deaminase ; genetics ; Animals ; Disease Models, Animal ; Mice ; Mice, Knockout ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Receptor, Notch1 ; genetics ; T-Lymphocytes

OBJECTIVE: To investigate the expressions of RNA-dependent adenosine deaminase 1(ADAR1) mRNA in larynx carcinoma tissues, and to discuss its value in the development of larynx carcinoma. METHOD: The expression of ADAR1 mRNA in 51 larynx carcinoma and peri-carcinoma tissues were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULT: ADAR1 mRNA was expressed broadly; the relative intensities of its expression in larynx carcinoma, larynx peri-carcinoma samples and larynx non-carcinoma tissue samples were respectively 2.963 +/- 0.912, 0.791 +/- 0.197 and 0.910 +/- 0.311. There were remarkable difference between larynx carcinoma and larynx peri-carcinoma, larynx carcinoma and non-carcinoma tissues. CONCLUSION ADAR1 mRNA is expressed broadly in larynx carcinoma and may be play an important role in the development of larynx carcinoma.
Adenosine Deaminase ; genetics ; metabolism ; Aged ; Female ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; RNA, Messenger ; genetics ; RNA-Binding Proteins

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities.

METHODSThree patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity.

RESULTSFamily pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on ADAR1 (c. 1325C>G) and one recurrent mutation in ABCB6 (c. 1270T>C), which successfully distinguished two diseases with the similar phenotype.

CONCLUSIONTargeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.

ATP-Binding Cassette Transporters ; genetics ; Adenosine Deaminase ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Child ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Pedigree ; Pigmentation Disorders ; congenital ; diagnosis ; genetics ; RNA-Binding Proteins ; genetics ; Skin Diseases, Genetic ; diagnosis ; genetics

With the development of the research on biotechnology and modern pharmacy, the application of enzyme drugs have grown rapidly and enzyme drugs have become an important branch of biopharmaceutics. In this article, some new varieties of therapeutic enzymes, enzyme targets, mechanisms and new technologies of application in therapeutic enzymes were reviewed, and the direction of development of therapeutic enzymes were discussed.
Adenosine Deaminase ; genetics ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Enzyme Replacement Therapy ; methods ; Fibrinolytic Agents ; therapeutic use ; Protein C ; genetics ; therapeutic use ; RNA, Catalytic ; genetics ; therapeutic use ; Streptokinase ; genetics ; therapeutic use ; Urokinase-Type Plasminogen Activator ; genetics ; therapeutic use