摘要:

AbstractType I (tyrosinase related) oculocutaneous albinism (OCA) results from mutations of the tyrosinase gene on chromosome 11q that lead to reduced or absent melanin pigment synthesis. The phenotype of Type I OCA is broad, ranging from a total lack to only a moderate reduction of melanin, and the phenotypic variation is associated with different mutant alleles at the tyrosinase locus. A total of 36 mutations have been identified in Type I OCA including 24 missense, 4 nonsense, and 8 frameshift mutations. The majority of affected individuals have been compound heterozygotes with different maternal and paternal alleles. Six polymorphic sites for haplotype analysis have been identified in the tyrosinase gene including 2 in the promoter region, 2 in the coding region associated with alternative amino acids in the protein, and 2 RFLPs in the first intron. © 1993 Wiley‐Liss, I

ISSN:1059-7794    

DOI:10.1002/humu.1380020102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractCystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 individuals seen at The Nebraska Regional Cystic Fibrosis Center that included 139 CF patients, 206 parents, and 55 unaffected siblings to determine the frequency of the ΔF508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that included XV‐2c, KM‐19, pMP6d.9, and G2. Results from this study showed that the ΔF508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the ΔF508 deletion, 47 (34%) were heterozygous for the ΔF508 deletion and an unknown mutation, and 18 (13%) carried two unknown mutations. Four additional‐mutations were also found in our population and included G542X (6%), G551D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that has previously been reported in several families was also present in our study. The most common haplotype associated with the ΔF508 deletion in our CF patients was the E haplotype (CF Consortium B) while other mutations were associated with a variety of haplotypes. © 1993 Wile

ISSN:1059-7794    

DOI:10.1002/humu.1380020103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have analysed 194 Belgian CF chromosomes using a variety of techniques: ΔF508 was detected by polyacrylamide gel electrophoresis; dot blotting of PCR products was used to identify the mutations G542X, 1717‐1 G → A, and N1303K; molecular defects in exons 2, 3, 4, 5, 6b, 7, 11, 12, 13, 14a, 14b, 17b, 19, 20, and 21 were screened for by DGGE. We identified 17 mutations, which accounted for 94.3% of the Belgian CF chromosomes. Four novel mutations and a novel polymorphism were characterized. The detection of such a high proportion of Belgian CF mutations is important in understanding the functional role of the molecule and in improving prenatal and genetic diagnosis of CF. © 1993 Wiley‐Li

ISSN:1059-7794    

DOI:10.1002/humu.1380020104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractIt has been proposed that the structure of the exons that encode the triple helical domain of the fibrillar collagen genes arose by repeated tandem duplication of an ancestral unit exon. Because these exons encode a repeat motif [(Gly‐X‐Y)n], sequence homology between exons may have driven the recombinational process. We have characterized a tandem duplication mutation within a COL1A1 allele of type I collagen from an infant with the lethal form of osteogenesis imperfecta. The structure of the mutation is consistent with the occurrence of an unequal crossover within a 15 base pair region of sequence identity between exons 14 and 17 of the COL1A1 gene. The recombination produced a new 81 base pair 17/14 hybrid exon and complete duplication of exons 15 and 16. The sequence implies duplication of 60 amino acid residues within the triple helical domain with preservation of the Gly‐X‐Y repeat. These data suggest that a recombinational mechanism that explains the hypothetical evolutionary process is active in cells, but the lethal effect of this mutation raises questions about the role of these events in creating new structures for polymeric proteins. © 1993 Wiley

ISSN:1059-7794    

DOI:10.1002/humu.1380020105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA single‐base mutation in intron 37 of the gene for type III procollagen (COL3A1) was found in a proband with the type IV variant of Ehlers—Danlos syndrome. Probe‐protection experiments with S1 nuclease and RNA from fibroblasts incubated at 37°C demonstrated that about 35% of the total mRNA or about 70% of the mRNA from mutated allele was spliced by exon skipping. The effects of the mutation were temperature‐sensitive in that the amount of RNA from the mutated allele that was spliced by exon skipping was 87.1 ± 7.7% at 31°C, 70.1 ± 6.5% at 37°C, and 85.4 ± 11.1% at 42°C. The effects of temperature on aberrant RNA splicing were, therefore, the reverse of those reported for four previous mutants incollagen genes. The increase in abnormal RNA splicing when the temperature was raised from 31° to 37°C seen with previously reported mutants suggested that RNA–RNA hybridization of U1snRNA to the 5′‐splice site in the substrate may be limiting in the processing of transcripts from the mutated alleles, since RNA–RNA hybridizations become less favorable at higher temperatures. The decrease in abnormal RNA splicing seen here when the temperature was raised from 31° to 37°C suggested that protein–RNA or protein–protein binding steps become rate limiting with the G+5mutation in intron 37 of the COL3A

ISSN:1059-7794    

DOI:10.1002/humu.1380020106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have identified a single base change in exon 4 of the type I keratin gene which results in the replacement of a methionine for an arginine residue at codon 272 in an Irish family displaying an autosomal dominant simplex (Koebner) form of epidermolysis bullosa (EB). This family had previously provided tentative evidence for linkage to genetic markers on chromosome 1q. The mutation cosegregates with the disease, producing a lod score of 4.8 at θ = 0. © 1993 Wiley‐Liss,

ISSN:1059-7794    

DOI:10.1002/humu.1380020107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have searched for mutations in the choroideremia gene (CHM) in patients from 12 Danish families in which CHM is segregating. Employing polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and direct DNA sequencing, different mutations have been identified in 6 patients. All the mutations will interfere with the correct translation of the mRNA predicting a truncated protein or no gene product at all. © 1993 Wiley‐Liss, I

ISSN:1059-7794    

DOI:10.1002/humu.1380020108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe sought to determine the spectrum of mutations producing β‐thalassemia in Egypt using genomic PCR and a variety of mutation‐screening procedures. Thirty‐four β‐thalassemia and three Hb S/β‐thalassemia patients originating from different regions of Egypt were studied, and the causative mutation was found in 69 of 71 (97%) β‐thalassemia genes. Four mutations accounted for 78% of β‐thalassemia genes in this population; IVS‐1, nt 110 (41%), IVS‐1 nt 6 (13%), IVS‐1, nt 1 (13%), and IVS‐2, nt 848 (11%). The latter allele, a C–A mutation at the third nucleotide of an acceptor site consensus sequence, has been described previously only in one Egyptian, one Iranian, one Tunisian, and one Black American patient. Nine other alleles each accounted for 1‐3% of β‐thalassemia genes. Among these was one codon 27 allele (Hb Knossos), two frameshift 106/107 alleles previously seen only in a Black American, and a rarely observed mutation in the distal promoter region of the β‐globin gene, −87 (C‐A). Our results suggest that from a molecular genetic standpoint a β‐thalassemia prevention program based on carrier screening and prenatal diagnosis can be implemented in Egypt. In couples at risk for β‐thalassemia, the causative mutation should be identifiable in both members in 92% and in one memb

ISSN:1059-7794    

DOI:10.1002/humu.1380020109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractHerein we report a 10.9 kb deletion and a 95 bp inversion in a patient with severe hemophilia B (factor IXHB209). With the addition of factor IXHB209, three of six characterized deletions in the factor IX gene are now known to include inversions. A high frequency of combined deletions and inversions has not previously been described in a human gene. © 1993 Wiley‐Liss, I

ISSN:1059-7794    

DOI:10.1002/humu.1380020110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA comparison was made between the 3 most commonly used techniques for the detection of point mutations: single‐strand conformation polymorphism (SSCP), constant denaturant gel electrophoresis (CDGE), and hydroxylamine and osmium tetroxide used in amplification mismatch cleavage analysis (HOT). Using human DNA samples containing known mutations in the p53 gene, SSCP detected 90% of mutations (18/20), CDGE detected 88% (15/17) pre‐decoding of the samples but 100% when the mutations were known and the CDGE conditions optimized, and the HOT technique was 100% accurate, although 1 mutation was missed through careless examination of the gel. The positive and negative aspects of each of the techniques are considered and suggestions are made regarding the particular situations in which each of them is most useful. © 1993 Wiley‐Lis

ISSN:1059-7794    

DOI:10.1002/humu.1380020111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY