Jimpy-4J Mouse Has a Missense Mutation in Exon 2 of the Plp Gene

1997 ◽  
Vol 19 (4) ◽  
pp. 337-341 ◽  
Author(s):  
Gail B. Pearsall ◽  
Nancy L. Nadon ◽  
Merrill K. Wolf ◽  
Susan Billings-Gagliardi
Keyword(s):  
Missense Mutation ◽  
Exon 2 ◽  
I Gene

scholarly journals GEN-03 GENOTYPE-PHENOTYPE CORRELATION IN 111 FAMILIES OF VON HIPPEL-LINDAU DISEASE IN JAPAN

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
Hiroshi Kanno ◽  
Tetsuya Yoshizumi ◽  
Masamichi Shinonaga ◽  
Masahiro Yao
Keyword(s):  
Amino Acids ◽  
Missense Mutation ◽  
Splice Site ◽  
Phenotype Correlation ◽  
Exon 2 ◽  
Endolymphatic Sac Tumor ◽  
Von Hippel Lindau ◽  
Genotype Phenotype Correlation ◽  
Exon 1 ◽  
Vhl Disease

Abstract BACKGROUND AND AIM von Hippel-Lindau (VHL) disease is a hereditary disease which manifest central nervous system (CNS) hemangioblastoma, retinal angioma, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumor, and pancreas cyst. The VHL gene is located at 3p25.3 and is corresponding to 213 amino acids. Genotype-phenotype correlation analyses of VHL disease have been recently reported from several foreign countries, but the genotype-phenotype correlation has not been characterized since above 10 years ago. Therefore, this study aimed to evaluate the VHL mutation spectrum and genotype-phenotype correlations in Japanese VHL patients. METHODS Blood samples of 111 unrelated families of VHL disease were collected and DNAs were extracted. Direct sequencing and real-time PCR analysis were performed. Consequently, the clinical manifestations and family histories of the subjects were evaluated. RESULTS We identified VHL mutations as follows: missense 47; deletion 17; insertion 5; nonsense 8; splice-site 9; larger deletion 25. At hot-spot codon 167, 4 minsense mutations were identified, with Arg167Trp, 4 cases; Arg167Gln2, 2 cases. At codon 155, splice-site mutations were identified at 6 cases. Mutation sites were distributed in exon 1, 45; exon 2, 21; exon 3, 36. Large deletions were distributed in exon 1 & 2, 1; exon 2& 3, 1; all exons, 11. Genotype-phenotype correlation analysis revealed that age-specific risk and number of CNS hemangioblastoma were significantly higher in subjects carrying missense mutation within HIF-α binding site or non-missense mutation (P < 0.05). In addition, penetrance of RCC was significantly higher in subjects carrying non-missense mutation (P < 0.05). CONCLUSIONS The results of this study were similar to the previous foreign studies. This study provides insight into the genotype-phenotype correlation in that amino acids substitutions in the HIF- α binding and non-sense mutations may predispose VHL patients to age-related risk and number of CNS hemangioblastoma.

scholarly journals Metabolic abnormalities in G6PC3-deficient human neutrophils result in severe functional defects

2020 ◽  
Vol 4 (23) ◽  
pp. 5888-5901
Author(s):  
Christopher McKinney ◽  
Michael Ellison ◽  
Natalie J. Briones ◽  
Angelina Baroffio ◽  
John Murphy ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Bacterial Infections ◽  
Neutrophil Function ◽  
Functional Improvement ◽  
Human Neutrophils ◽  
Compound Heterozygous ◽  
Cd11b Expression ◽  
Exon 2 ◽  
Metabolic Defects ◽  
Functional Defects

Abstract Severe congenital neutropenia type 4 (SCN-4) is an autosomal recessive condition in which mutations in the G6PC3 gene encoding for the catalytic 3 subunit of glucose-6-phosphatase-β result in neutropenia, neutrophil dysfunction, and other syndromic features. We report a child with SCN-4 caused by compound heterozygous mutations in G6PC3, a previously identified missense mutation in exon 6 (c.758G>A[p.R235H]), and a novel missense mutation in exon 2 (c.325G>A[p.G109S]). The patient had recurrent bacterial infections, inflammatory bowel disease, neutropenia, and intermittent thrombocytopenia. Administration of granulocyte colony–stimulating factor (G-CSF) resolved the neutropenia and allowed for detailed evaluation of human neutrophil function. Random and directed migration by the patient’s neutrophils was severely diminished. Associated with this were defects in CD11b expression and F-actin assembly. Bactericidal activity at bacteria/neutrophil ratios >1:1 was also diminished and was associated with attenuated ingestion. Superoxide anion generation was <25% of control values, but phox proteins appeared quantitatively normal. Extensive metabolomics analysis at steady state and upon incubation with stable isotope–labeled tracers (U-13C-glucose, 13C,15N-glutamine, and U-13C-fructose) demonstrated dramatic impairments in early glycolysis (hexose phosphate levels), hexosemonophosphate shunt (required for the generation of the NADPH), and the total adenylate pool, which could explain the dramatic cell dysfunction displayed by the patient’s neutrophils. Preliminary experiments with fructose supplementation to bypass the enzyme block demonstrated that the metabolic profile could be reversed, but was not sustained long enough for functional improvement. In human deficiency of G6PC3, metabolic defects resulting from the enzyme deficiency account for diverse neutrophil functional defects and present a major risk of infection.

scholarly journals Missense Mutation in Exon 2 of SLC36A1 Responsible for Champagne Dilution in Horses

PLoS Genetics ◽  
2008 ◽  
Vol 4 (9) ◽  
pp. e1000195 ◽  
Author(s):  
Deborah Cook ◽  
Samantha Brooks ◽  
Rebecca Bellone ◽  
Ernest Bailey
Keyword(s):  
Missense Mutation ◽  
Exon 2

Growth hormone induces tyrosine phosphorylation but does not alter insulin-like growth factor-I gene expression in human IM9 lymphocytes

1994 ◽  
Vol 13 (2) ◽  
pp. 127-136 ◽  
Author(s):  
P E Clayton ◽  
R N Day ◽  
C M Silva ◽  
P Hellmann ◽  
K H Day ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tyrosine Phosphorylation ◽  
Northern Hybridization ◽  
Mrna Levels ◽  
Transduction Pathway ◽  
Exon 2 ◽  
Early Protein ◽  
Its Gene ◽  
Igf I ◽  
I Gene

ABSTRACT GH induces hepatic IGF-I synthesis by increasing transcription of its gene. IGF-I is synthesized, however, in many other tissues where the effect of GH on its gene expression is less well characterized. IGF-I and GH are produced by human lymphocytes and may function as autocrine regulators of lymphoproliferation. We have therefore used the human IM9 lymphocyte cell line to (A) define the IGF-I gene transcripts expressed and (B) investigate the effect of GH on early (protein tyrosine phosphorylation) and late (changes in IGF-I mRNA levels) events in intracellular signal transduction. Multiple IGF-I mRNA species, ranging in size from 0·9 to 5·8 kb, were detected by Northern hybridization of poly(A)+ mRNA from IM9 cells. The human IGF-I gene contains at least six exons and alternative splicing produces a number of transcripts. Solution hybridization with exon-specific riboprobes and amplification by PCR using exon-specific primers revealed that multiple transcripts were expressed in IM9 cells, and that exon 2 was the dominant leader exon. Treatment of IM9 cells with 200 ng recombinant human (rh)GH/ml led to the specific tyrosine phosphorylation of three intracellular proteins (93, 120 and 134 kDa), which are involved in the initial signalling of the GH transduction pathway. However a solution hybridization assay using the IGF-IA specific riboprobe on IM9 cell RNA from similar experiments revealed that GH treatment did not change IGF-I gene expression. This study has demonstrated (A) that the IGF-I gene is expressed in human IM9 lymphocytes, (B) that in contrast to other human tissue, exon 2 is the major leader exon, and (C) that rhGH induces tyrosine phosphorylation of 93, 120 and 134 kDa proteins but does not alter IGF-I gene expression. The IM9 cell may form an important model to investigate a GH transduction pathway not coupled to the IGF-I gene.

scholarly journals Organization of the human β-1,2-N-acetylglucosaminyltransferase I gene (MGAT1), which controls complex and hybrid N-glycan synthesis

1997 ◽  
Vol 321 (2) ◽  
pp. 465-474 ◽  
Author(s):  
Betty YIP ◽  
Shi-Hao CHEN ◽  
Hans MULDER ◽  
Jo W. M. HÖPPENER ◽  
Harry SCHACHTER
Keyword(s):  
Genomic Dna ◽  
Transient Transfection ◽  
Transcription Start ◽  
Exon 2 ◽  
Transcription Start Sites ◽  
Exon 1 ◽  
Dna Fragment ◽  
Flanking Region ◽  
Ribonuclease Protection ◽  
I Gene

UDP-GlcNAc:α-3-d-mannoside α-1,2-N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-T I) is a medial-Golgi enzyme which catalyses the first step in the conversion of oligomannose-type to N-acetyl-lactosamine- and hybrid-type N-glycans and is essential for normal embryogenesis in the mouse. Previous work indicated the presence of at least two exons in the human GlcNAc-T I gene MGAT1, exon 2 containing part of the 5ƀ untranslated region and the complete coding and 3ƀ untranslated regions, and exon 1 with the remainder of the 5ƀ untranslated region. We now report the cloning and sequencing of a human genomic DNA fragment containing exon 1, which is between 5.6 and 15 kb upstream of exon 2. Transient transfection, ribonuclease protection and reverse transcriptase-mediated PCR indicated the absence of transcription start sites in intron 1 between exons 1 and 2. Northern analysis, ribonuclease protection, primer extension analysis and rapid amplification of 5ƀ-cDNA ends showed that there are multiple transcription start sites for exon 1 compatible with the expression by several human cell lines and tissues of two transcripts, a broad band ranging in size from 2.7 to 3.0 kb and a sharper band at 3.1 kb. The 5ƀ flanking region of exon 1 has a GC content of 81% and has no canonical TATA or CCAAT boxes but contains potential binding sites for transcription factors Sp1, GC-binding factor and epidermal growth factor receptor-specific transcription factor. Chloramphenicol acetyltransferase (CAT) expression was observed on transient transfection into HeLa cells of a fusion construct containing the gene for CAT and a genomic DNA fragment from the 5ƀ flanking region of exon 1. It is concluded that MGAT1 is a typical housekeeping gene although there is, in addition, tissue-specific expression of the larger 3.1 kb transcript.

ISOLATION AND IDENTIFICATION OF MHC-DRB GENE EXON 2 IN THE YANGTZE FINLESS PORPOISE

2009 ◽  
Vol 33 (5) ◽  
pp. 804-810
Author(s):  
He-Jun DU ◽  
Jin-Song ZHENG ◽  
Min WU ◽  
Qing-Zhong ZHAO ◽  
Ding WANG
Keyword(s):  
Finless Porpoise ◽  
Isolation And Identification ◽  
Mhc I ◽  
Exon 2 ◽  
Yangtze Finless Porpoise ◽  
Gene Exon ◽  
I Gene
Sign in / Sign up

Export Citation Format

Share Document