[Mutation of the alpha-galactosidase A gene in two unusual variations of Fabray's disease].
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The mutation analysis of alpha-galactosidase A gene was carried out in two families with Fabry disease described by us earlier. In the family P. a new point mutation E341K (a G to A transition at position 10,999 of the gene) was identified. The mutation causes a Glu341Lys substitution in alpha-galactosidase A molecule. Another point mutation was identified in a patient from family N. who had unusual unusually high residual activity of alpha-galactosidase A. The mutation was identified as R112C (a C to T transition at position 5233 of alpha-galactosidase A gene) and it caused the Arg112Cys substitution in the enzyme molecule. This mutation was earlier described in Japanese patient with showed a complete loss of enzyme activity. However, in this case the mutation was combined with another mutation Glu66Gln. The relationship between genetic heterogeneity and clinical manifestation of Fabry disease is discussed.Keywords:
Alpha (finance)
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Alpha-galactosidase
Mutation Testing
High Resolution Melt
Cytosine
Alpha (finance)
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Objective To detect the mutation of DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria (DSH), and to explore new pathogenic mutation. Methods Members of a Chinese family with DSH, who had typical rash, were enrolled in this study, with normal physical development and intelligence, no obvious systematic symptoms. RT-PCR was applied to obtain DSRAD gene cDNA from human peripheral blood. Proper gene sequences were selected and compared with corresponding gene of human gene pool to identify suspicious sites, and new mutations were validated by single strand conformation. Results DSRAD gene sequence analysis confirmed the presence of nucleotide substitutions in the patient's chromosomes, with Q389Q replaced by A1167G. The encoding amino acid was still glutamic acid, which indicated a synonymous mutation. Single strand conformation confirmed that the DNA of the patients was of the same family, and that the healthy members and non-kinship members were not detected with the coding gene. Conclusion The abnormal changes of skin pigment may be due to synonymous mutations in gene. The mutation mechanism still needs further study.
Mutation Testing
Coding region
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The mutation analysis of alpha-galactosidase A gene was carried out in two families with Fabry disease described by us earlier. In the family P. a new point mutation E341K (a G to A transition at position 10,999 of the gene) was identified. The mutation causes a Glu341Lys substitution in alpha-galactosidase A molecule. Another point mutation was identified in a patient from family N. who had unusual unusually high residual activity of alpha-galactosidase A. The mutation was identified as R112C (a C to T transition at position 5233 of alpha-galactosidase A gene) and it caused the Arg112Cys substitution in the enzyme molecule. This mutation was earlier described in Japanese patient with showed a complete loss of enzyme activity. However, in this case the mutation was combined with another mutation Glu66Gln. The relationship between genetic heterogeneity and clinical manifestation of Fabry disease is discussed.
Alpha (finance)
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We have applied single-strand conformation polymorphism (SSCP) to the analysis of exon 7 of the anticoagulant protein C (PC) gene, in 13 PC-deficient Spanish families. Abnormal patterns were visualized in three samples from type I or quantitative PC deficient proposita. A previously undescribed mutation due to a TT insertion after nucleotide 6139, between codons Gly-142 and Arg-143 was found in one family. The mutation (6139,ins TT) should result in a frameshift with a stop at codon 156, which agrees with the presence of a type I or quantitative PC deficiency in the affected members of the family. The second mutation identified was a C to T transition at nucleotide 6274, 9 base pairs into intron G. This mutation (6274,C-->T), found for the first time in a Spanish family, is identical to the previously characterized PC Sant Louis. The third mutation was a G to A transition that replaces arginine 178 with glutamine (178,R-->Q). This is the third case of 178,R-->Q mutation in 17 apparently unrelated Spanish families with type I PC deficiency. Furthermore, SSCP analysis allowed the detection of another previously described mutation in a PC-deficient Spanish family (178,R-->W).
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Insertion
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To learn the variation in the gene for UGT1A1 enzyme, the genetic mechanism in a Chinese Han nationality family suffered from Gilbert's syndrome was studied. At first, genomic DNA from peripheral blood of the sufferer in this family was used for amplifying all of the five exons of the UGT1A1 gene by PCR, and then direct sequencing of the PCR product was applied to analyze gene mutation. The results showed that there existed a G-->A homozygous transition at nucleotide 211 leading the substitution of arginine for glycine at position 71 of corresponding protein product (G71R) and a T-->G homozygous transition at nucleotide 1456 leading the substitution of aspartic acid for tyrosine at position 486 of corresponding protein product (Y486D). No mutation was detected in promoter region and the splicing junction sites. The relevant mutation sites of the other family members were sequenced and identified to be heterozygous in the two above-mentioned mutation sites and in the TA repeat mutation in the promoter region. Furthermore, fresh blood samples were collected from all of the members to detect the serum bilirubin levels to determine the sufferer. The result was consistent with the mutation analysis. It could thus be inferred that this family was caused by mutation in the open reading frame of the gene UGT1A1.
Mutation Testing
genomic DNA
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Objective To detect the gene mutation and mutation effect in a Chinese pedigree with osteogenesis imperfecta (OI) and to lay a foundation for the research of mutation characteristics of OI in Chinese population. Methods A genome screen was undertaken covering COL1A1 at 17q21-22 and COL1A2 at 7q22.1 and the Linkage was used for 2-point analysis. The pathogenic gene was preliminarily decided. The pathogenic gene exon was amplified with DNA, and DNA sequencing was used to screen and identify the mutation.Results COL1A1 mutation was detected in this pedigree. Sequence analysis of COL1A1 revealed a splicing mutation (IVS8-2AG) that converted the 3' end of intron 8 from AG to GG. Conclusion This mutation (IVS 8-2AG) is novel, which has not yet been registered in the COL1A1 mutations database.
Mutation Testing
Chinese population
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To detect genetic mutations associated with autosomal dominant congenital stationary night blindness (ADCSNB) in a family from Henan province.Genomic DNA was extracted from peripheral blood samples of 14 family members. Based on 3 genes reported previously, PCR primers were designed and corresponding exons containing the mutation sites were amplified with PCR. PCR products were purified and directly sequenced.A c.281C>T heterozygous missense mutation was detected in RHO gene in all of the patients. This mutation can cause a change of the protein structure (p.Thr94Ile). The same mutation was not detected in normal individuals from the family and 50 normal controls.A c.281C>T mutation in RHO gene is responsible for the onset of ADCSNB in this Chinese family and results in symptoms of night blindness.
genomic DNA
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Nonsense mutation
GTP cyclohydrolase I
Coding region
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Hemophilia A is a bleeding disorder caused by a quantitative or qualitative deficiency in the coagulation factor VIII. Causative mutations are heterogeneous in nature and are distributed throughout the FVIII gene. With the exception of mutations that result in prematurely truncated protein, it has proved difficult to correlate mutation type/amino acid substitution with severity of disease. We have identified 81 mutations in 96 unrelated patients, all of whom have typed negative for the common IVS-22 inversion mutation. Forty-one of these mutations are not recorded on F8C gene mutation databases. We have analyzed these 41 mutations with regard to location, whether or not each is a cross-species conserved region, and type of substitution and correlated this information with the clinical severity of the disease. Our findings support the view that the phenotypic result of a mutation in the FVIII gene correlates more with the position of the amino acid change within the 3D structure of the protein than with the actual nature of the alteration.
Amino acid substitution
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