Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MUTATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2000

Screening for mutations in exon 4 of the LDL receptor gene in Thai subjects with primary hypercholesterolemia: detection of a novel mutation D151Y by PCR-CFLP.

A mutation in low density lipoprotein (LDL) receptor gene causes an autosomal codominant disorder namely familial hypercholesterolemia (FH). Mutations in the LDL receptor gene are very heterogeneous at the DNA levels, occurring in all 18 exons of the gene. However, exon 4 has been found to be the hot spot for mutational events. In this study DNA from 45 Thai subjects with primary hypercholesterolemia was screened for mutations in the hot spot exon 4. The DNA samples were amplified by Polymerase Chain Reaction (PCR) and screened for mutation by Cleavase Fragment Length Polymorphism (CFLP) technique. Identification of mutation was performed by direct sequencing of PCR product. From this screening, one female patient was found to be heterozygous for a novel mutation which was due to a G to T transversion at nucleotide 514. This transversion would change the species-conserved amino acid at codon 151 from charged R group aspatic (GAC) to uncharged R group tyrosine (TAC), termed D151Y. From the same screening strategy, we found that this mutation was absent in 33 healthy normolipidemic subjects. In this index subject, Arg 3500 Gln mutation in apo B-100 gene, causing hypercholesterolemia namely familial defective apo B-100 (FDB), was not found. Therefore, hypercholesterolemia in this index subject was possibly caused by the D151Y mutation in the LDL receptor gene.

DNA Mutational Analysis↗
PubMed1994

p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis.

We determined the pattern of mutations in exons 2-11 and adjacent intronic regions in breast cancers from Midwestern US white women. Twenty-one mutations were detected in 53 tumors (39.6%). Comparisons of the pattern of mutations within exons 5-9 showed that the frequency of missense mutations (44%) was lower in breast cancers of US Midwestern women than in most tumor types including breast cancers in other populations. Compared to breast cancers reported in a Scottish population, US women had a high frequency of G:C-->T:A transversions (P = 0.046). These findings suggest that environmental or endogenous factors contribute to p53 mutagenesis in mammary tissue to different extents among different populations. With a median follow-up of 19 months, the presence of a mutation was associated with shorter time to disease recurrence (P = 0.05) and shorter survival (P = 0.003). Putative dominant negative missense-type mutations (missense and in-frame microdeletions; P = 0.001) and null mutations (hemizygous nonsense and frameshift mutations; P = 0.007) were equally ominous. Thus, tumors with missense p53 mutations resulting in over-expression of a dysfunctional but otherwise intact protein have a clinical outcome similar to tumors with null mutations resulting in a truncated or garbled protein.

Adult↗
PubMed1999

Mutation analysis in adenylosuccinate lyase deficiency: eight novel mutations in the re-evaluated full ADSL coding sequence.

The deficiency of adenylosuccinate lyase (ADSL, also termed adenylosuccinase) is an autosomal recessive disorder characterized by the accumulation in body fluids of succinylaminoimidazole-carboxamide riboside (SAICA-riboside) and succinyladenosine (S-Ado). Most ADSL-deficient children display marked psychomotor delay, often accompanied by epilepsy or autistic features, or both, although some patients may be less profoundly retarded. Occasionally, growth retardation and muscular wasting are also present. Up to now, nine missense mutations of the ADSL gene had been reported in six apparently unrelated sibships. In the present study of 10 additional patients with ADSL deficiency, nine point mutations, among which seven unreported missense mutations, and the first splicing error reported in this disorder, have been identified. These mutations have been characterized, taking into account the finding that the cDNA of human ADSL is 75 nucleotides longer at its 5'-end, and encodes a protein of 484 rather than 459 amino acids as previously reported. Five apparently unrelated patients were found to carry a R426H mutation. With the exceptions of the latter mutation, of a R190Q mutation that had been reported previously, and of a K246E mutation that was found in two unrelated patients, all other mutations were found only in a single family.

Adenylosuccinate Lyase↗
PubMed1996

Molecular characterization of mutation and comparison of mutation profiles in the hprt gene of Chinese hamster ovary cells treated with benzo[a]pyrene trans-7,8-diol-anti-9,10-epoxide, 1-nitrobenzo[a]pyrene trans-7,8-diol-anti-9,10-epoxide, and 3-nitrobenzo[a]pyrene trans-7,8- diol-anti-9,10-epoxide.

Both 1- and 3-nitrobenzo[a]pyrene (nitro-BaP) are environmental contaminants, potent mutagens in Salmonella, and moderate mutagens in Chinese hamster ovary (CHO) cells. The mutagenicity of their oxidized metabolites,trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-epoxy -7,8,9,10-tetrahydro-1-nitrobenzo[a]pyrene (1-nitro-BaP-DE) and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo[a]- pyrene (3-nitro-BaPDE), together with trans-7,8-dihydroxy-anti-9, 10-ep- oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP-DE), was determined in CHO-K1 cells, and the resulting mutations at the hprt locus were characterized by polymerase chain reaction (PCR) amplification of reverse-transcribed hprt mRNA, followed by DNA sequence analysis. The mutant frequencies, in mutants/10(6) clonable cells, at 30 and 100 ng/ml, were BaP-DE, 248 and 456; 1-nitro-BaP-DE, 68 and 260; 3-nitro-BaP-DE, 81 and 232, respectively. In general, the three diolepoxides exhibited similar mutational spectra: 1) 64% (23/36 sequenced mutants) of BaP-DE, 53% (19/36) of 1-nitro-BaP-DE, and 64% (23/36) of 3-nitro-BaP-DE mutants resulted from simple base pair substitution, with the predominant mutation being G-->T transversion; 2) 90%, 100%, and 100% of mutations at G:C had the mutated dG on the nontranscribed DNA strand; and 3) about one quarter of the mutants produced by each mutagen had one or more PCR products with partial or complete exon deletions. The mutagens induced few frameshifts or complex mutations. Among the differences in mutational specificity for the three diolepoxides, the proportion of substituted dGs with 3' purines was significant (P < 0.05) for BaP-DE (16/19, 84%) and 3-nitro-BaP-DE (17/20, 85%), but not significant for 1-nitro-BaP-DE-induced mutants (11/17, 65%, P > 0.05). Also, high proportions of BaP-DE and 3-nitro-BaP-DE base pair substitutions at G:C occurred in DNA sequence contexts of 5'-GG-3', 5'-GGA-3', and 5'-TGGA-3', while the proportions of 1-nitro-BaP-DE mutants in these contexts were often lower. The results indicate that nitro substitution at C1 or C3 of BaP-DE reduces mutational potency in CHO cells and appears to have only subtle effects upon the mutational pattern in the hprt gene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2007

Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene.

Straightforward detectable Duchenne muscular dystrophy (DMD) gene rearrangements, such as deletions or duplications involving an entire exon or more, are involved in about 70% of dystrophinopathies. In the remaining 30% a variety of point mutations or "small" mutations are suspected. Due to their diversity and to the large size and complexity of the DMD gene, these point mutations are difficult to detect. To overcome this diagnostic issue, we developed and optimized a routine muscle biopsy-based diagnostic strategy. The mutation detection rate is almost as high as 100% and mutations were identified in all patients for whom the diagnosis of DMD and Becker muscular dystrophy (BMD) was clinically suspected and further supported by the detection on Western blot of quantitative and/or qualitative dystrophin protein abnormalities. Here we report a total of 124 small mutations including 11 nonsense and frameshift mutations detected in BMD patients. In addition to a comprehensive assessment of muscular phenotypes that takes into account consequences of mutations on the expression of the dystrophin mRNA and protein, we provide and discuss genomic, mRNA, and protein data that pinpoint molecular mechanisms underlying BMD phenotypes associated with nonsense and frameshift mutations.

Adolescent↗
PubMed2006

Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies.

GM1-gangliosidosis and Morquio B disease are rare lysosomal storage disorders caused by beta-galactosidase deficiency due to mutations in the GLB1 gene. Three major clinical forms of GM1-gangliosidosis have been established on the basis of age of onset and severity of symptoms: infantile, late infantile/juvenile, and adult. We performed mutation analysis on 30 GM1-gangliosidosis and five Morquio B patients, mainly of Spanish origin, and all the causative mutations were identified. Thirty different mutations were found, 21 of which were novel. With the exception of two adults and one juvenile patient, all the GM1-gangliosidosis patients were affected by the infantile form. Clinical findings are presented for all patients. We report the association of the novel mutations p.T420K and p.L264S with the adult form and the juvenile form, respectively. In addition, the novel mutation p.Y83C was associated with Morquio B disease. Among the 30 GM1-gangliosidosis patients, 6 were of Gypsy origin (Roma). Moreover, those six Gypsy patients shared not only the same mutation (p.R59H) but also a common haplotype. This observation indicates a possible founder effect in this group and suggests that screening of the p.R59H mutation may be appropriate in GM1-gangliosidosis patients of Gypsy origin. This is the first exhaustive mutational analysis performed in a large group of Iberian GM1-gangliosidosis and Morquio B patients.

Adolescent↗
PubMed2001

Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations.

Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (DeltaF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G --> T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant DeltaF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity.

Adult↗
PubMed2001

Mutation analysis and the correlation between genotype and phenotype of Arg778Leu mutation in chinese patients with Wilson disease.

BACKGROUND: The defective gene (ATP7B) that causes Wilson disease (WD) codes for a putative copper-transporting P-type adenosine triphosphatase. After cloning of ATP7B, the spectrum of mutations and their clinical consequences have been investigated in patients with WD in different ethnic populations. However, the spectrum of mutations and the correlation of genotype-phenotype in the Chinese population have not been extensively studied. OBJECTIVE: To investigate the characterization of mutations of ATP7B and the correlation between genotype and phenotype in the Chinese population. METHODS: We studied 60 unrelated healthy Chinese and 65 unrelated Chinese families, including 84 patients with WD and 126 parents. Genomic DNA was prepared from peripheral blood leukocytes using a salt-precipitation method. Polymerase chain reaction single-strand conformation polymorphism and subsequent direct sequencing were used to identify the mutations and polymorphisms of ATP7B. Statistical analysis was performed using t test or chi(2) test. RESULTS: We identified 18 mutations (7 novel) and 11 polymorphisms (3 novel). The novel mutations are -36C-->T, Trp650ter, Gln914ter, 2810delT, Thr935Met, Arg1041Pro, and Glu1173Lys. The novel polymorphisms are 1168A-->G (Ile390Val), 2785A-->G (Ile929Val), and 3316G-->A (Val1106Ile). Two mutations, Arg778Leu and Thr935Met, are relatively frequent, representing 37.7% and 10.0% of patients, respectively. To our knowledge, we are the first to report the correlation between the genotype and phenotype of Arg778Leu. The result shows that Arg778Leu homozygotes are associated with the early onset of WD with hepatic presentation. CONCLUSIONS: The Arg778Leu and Thr935Met mutations are hot spots in the Chinese population. The features of mutations of ATP7B differ between the Chinese and Western ethnic populations. The Arg778Leu mutation has severe effects on the function of ATP7B. These findings are valuable for developing a fast and effective method to diagnose the presence of the WD gene.

Adolescent↗
PubMed1996

Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines: increased frequency and different spectrum of mutations from primary tumors.

We screened 29 human esophageal squamous cell carcinoma (ESC) cell lines for mutations of the p53 gene through all coding exons and exon-intron junctions. Mutations were found in 22 cell lines (76%), consisting of 20 single-base substitutions, 2 small deletions and 1 single-base insertion. Out of 20 single-base substitution, 5 were located at the exon-intron junctions and mRNAs with abnormal splicing were detected by RT-PCR in 4 of them. A G:C to T:A transversion, which occurred rather frequently in resected tumors of ESC, was observed in only 1 cell line, and, instead, frequent transitions at CpG sites were detected. We also examined 65 fresh tumor materials, from all of which we tried to establish cell lines, and detected mutations in 26 samples (40%). Compared with the results in these fresh tumor materials, the mutation incidence in cell lines was significantly high and the mutation spectrum was also different. From these 65 tumors, 10 cell lines were established, including 3 cell lines from 26 tumors with p53 mutations and 7 cell lines from 39 without mutations, which indicates that there was no significant correlation between the status of the p53 gene in each fresh tumor and its establishment as a cell line. In 7 cell lines established from mutation-free tumors, newly acquired mutations were detected in 5, which suggests that mutations might occur during the process of establishing cell lines.

Base Sequence↗
PubMed1998

Four new mutations in the DNA mismatch repair gene MLH1 in colorectal cancers with microsatellite instability. Mutations in brief no. 157. Online.

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with inherited mutation in one of four DNA mismatch repair genes. Somatic mutations in the same genes are also found in a subset of sporadic colorectal cancers. A defect in DNA mismatch repair results in a RER (replication error) tumor phenotype. We screened 110 archival and 11 prospectively acquired colorectal cancers for the RER phenotype. A total of 22 cancers were RER-positive. RER-positive tumors were investigated for mutations in the DNA mismatch repair gene MLH1 using single-strand-conformation-polymorphism (SSCP) analysis. We identified four previously undescribed mutations in four different samples. Three mutations were exonic: a point mutation at codon 69 (AGG-->AAG(arg-->lys]); a single base pair deletion at codon 42/43 (GCAAAATCC-->GCAAATCC) leading to a new stop codon downstream; and a point mutation at codon 757 (TAA-->TAT [termination-->tyr] which extend the MLH1 peptide by 36 ammino acids. The fourth mutation was a 1 base pair insertion six base pairs 5' to the start of exon 14 (tttgtttt-->tttggtttt). The mutations were not seen in the patients' constitutional DNA. The somatic MLHI mutations identified appear to be causally associated with the RER phenotype.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Factor IX mutations in South Africans and African Americans are compatible with primarily endogenous influences upon recent germline mutations.

Similar patterns of germline mutations in the factor IX gene (F9) have been observed in certain geographically and racially diverse populations. Germline mutation data have not been available from any region of Africa or from the Black race. Analysis of mutation data for Blacks is of interest, since this race has a high frequency of polymorphism compared to other races. This high frequency has been interpreted as evidence for the "out of Africa" hypothesis for the origin of humans, but it is possible that Blacks have a higher mutation rate due to genetic differences or environmental exposures. We report 26 independent mutations that were detected in patients of mixed races with hemophilia B from South Africa. The pattern of mutation in patients from this African country was similar to that of U.S. Caucasians. In addition, 22 independent mutation were detected in African American patients. The patterns of independent germline mutation in 22 African Americans (and in a combination 34 North American and African Blacks) is similar to that of U.S. Caucasians. Neither genetic differences between the Black and Caucasian races nor environmental and cultural differences between South Africa and the U.S. alter the germline pattern of mutation observed in F9. Hum Mutat 16:372, 2000.

Black People↗
PubMed2000

BTK mutations in patients with X-linked agammaglobulinemia: lack of correlation between presence of peripheral B lymphocytes and specific mutations.

X-linked agammaglobulinemia (XLA) is a human antibody deficiency that results from mutation of the tyrosine kinase btk. We tested the hypothesis that XLA patients who varied from the classic phenotype of XLA by presence of normal or near normal number of peripheral B lymphocytes would have a set of mutations of BTK that is different from the mutations found in patients without peripheral B lymphocytes. The mutations of BTK we found in two patients with normal numbers of peripheral B lymphocytes have been previously identified in patients without peripheral B lymphocytes. A third patient, without peripheral B cells, was found to express normal levels of wild type btk. Exmination of the mutations of the BTK gene in patients in the BTKbase who were identified as having peripheral B lymphocytes found that these same mutations, or mutations of the same protein domains, were also present in patients identified as lacking peripheral B lymphocytes. Analysis of mutations in BTK has previously led to the conclusion that severity of disease in XLA cannot be predicted from the specific mutation of BTK. The results of this study suggest that whether an XLA patient will develop peripheral B lymphocytes cannot be predicted from the specific mutation of BTK.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human.

Spontaneous mutation rates per generation are similar among the three species considered here--Drosophila, mouse, and human--and are not related to time, as is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they are among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation are: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9-month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-day generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the soma from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions.

Animals↗
PubMed2002

Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.

Cystinosis is an autosomal recessive disorder characterized by intra-lysosomal accumulation of cystine. Three disease forms exist, infantile, juvenile, and ocular nonnephropathic cystinosis, delineated on the basis of severity of symptoms and age of onset. Mutations in the causative gene, CTNS, which encodes cystinosin, the seven transmembrane domain lysosomal cystine transporter, have been identified in all forms confirming their allelic status. By screening for mutations in the CTNS exons and promotor region, we report 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, two juvenile cystinosis, and one associated with an atypical form of the disease. These mutations, all situated in the exons or immediately flanking intronic sequences, comprise in-frame insertions and deletions, as well as missense, nonsense, and putative splice-site mutations. Furthermore, we confirmed the putative splice-site mutations we have reported to date (five novel and two previously reported) by isolation of RNA from the affected carriers and characterization of the resultant transcripts using RT-PCR. Since the cloning of CTNS, we have screened for mutations in 108 affected individuals, which has resulted in a high mutation detection rate of 95.8%. Interestingly, the few undetectable mono- or bi-allelic mutations segregated mostly in the noninfantile forms, suggesting that these individuals carry mutations either in the introns or in unidentified regulatory sequences.

Adolescent↗
PubMed2004

Y-chromosomal microsatellite mutation rates: differences in mutation rate between and within loci.

Precise estimates of mutation rates at Y-chromosomal microsatellite STR (short tandem repeat) loci make an important basis for paternity diagnostics and dating of Y chromosome lineage origins. There are indications of considerable locus mutation rate variability between (inter-) and within (intra-) loci. We have studied nine Y-STR loci-DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385, and DYS388-in 1,766 father-son pairs of confirmed paternity (a total of 15,894 meioses). Five biallelic markers were also analyzed in the fathers-Tat, YAP, 12f2, SRY1532, and 92R7-defining haplogroups 1, 2, 3, 4, 9, and 16, respectively. A total of 36 fragment length mutations were observed: 24 gains (22 single-step, two double-step) and 12 single-step losses. Thus, there was a significant surplus of gains (p=0.045). Overall, the mutation rate was positively correlated to STR repeat length and there was a significant relative excess of losses in long alleles and gains in short alleles (p=0.043). In contrast to the situation in autosomal STR loci and in MSY-1, no noteworthy correlation between mutation rate and the father's age at the child's birth was observed. We observed significant interlocus differences in Y-STR mutation rates (p<0.01). The number of observed mutations ranged from zero in DYS392 to eight in DYS391 and DYS390. We have also demonstrated obvious differences in mutation rates between the haplogroups studied (p=0.024), a phenomenon that is a reflection of the dependence of mutation rate on allele size. Our study has thus demonstrated the necessity of not only locus-specific, but even allele-specific, mutation rate estimates for forensic and population genetic purposes, and provides a considerable basis for such estimates.

Adolescent↗
PubMed2005

Beta-catenin mutations and expression, 249serine p53 tumor suppressor gene mutation, and hepatitis B virus infection in southern African Blacks with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: To ascertain the prevalence of deregulating mutations of beta-catenin gene, and to correlate this with the occurrence of 249(serine) p53 gene mutation and hepatitis B virus infection in southern African Blacks with hepatocellular carcinoma. METHODS: Paired cancer/non-cancerous liver tissues from 21 and cancer tissues alone from 20 Black Africans with hepatocellular carcinoma were studied. RT-PCR-SSCP and sequencing were used to detect mutations in exon 3 of the beta-catenin gene, and PCR, restriction endonuclease analysis, and sequencing to detect the p53 gene mutation. Immunostaining was used to identify beta-catenin protein expression in hepatocytes. RESULTS: No mutations in exon 3 of the beta-catenin gene were found in tumor or non-tumorous tissues. Immunohistochemical staining showed beta-catenin protein expression in membranes and cytoplasm of hepatocytes but not in the nuclei. The 249serine p53 gene mutation was detected in 27.2% of the hepatocellular carcinoma tissues but not in non-cancerous tissues. No correlation was found between beta-catenin mutation and over-expression and 249serine p53 gene mutations or hepatitis B virus surface antigenemia. CONCLUSIONS: Unlike hepatocellular carcinomas in China, Japan, and Europe, deregulating beta-catenin gene mutations do not appear to occur in southern African Blacks with this tumor and do not therefore interact with either the 249serine p53 gene mutation or hepatitis B virus infection in its pathogenesis.

Africa, Southern↗
PubMed2003

Mutational analysis of BRAF and K-ras in gastric cancers: absence of BRAF mutations in gastric cancers.

Recently, BRAF mutations were found in a variety of human cancers. Interestingly, the most common of BRAF mutation (V599E) has not been identified in tumors with K-ras mutations. Whereas the majority of human cancer types has been screened for BRAF mutations, no detailed studies on gastric cancers have been investigated. Thus, we decided to investigate the incidence of BRAF mutations in gastric cancers, and the relationship between BRAF and K-ras mutations in such cancers. Three non-pathogenic BRAF polymorphisms and seven K-ras missense mutations were found in 66 gastric cancers and 16 gastric cancer cell lines. Although only 9% of our gastric cancer panels had K-ras mutations, the incidence of BRAF mutations was not high. Thus, BRAF mutations, which are present in a variety of other human cancers, do not seem to be involved in gastric cancer development.

Base Sequence↗
PubMed1996

Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disease caused by mutation in the recently isolated gene encoding WAS protein (WASP), is known to be associated with extensive clinical heterogeneity. Cumulative mutation data have revealed that WASP genotypes are also highly variable among WAS patients, but the relationship of phenotype with genotype in this disease remains unclear. To address this issue we characterized WASP mutations in 24 unrelated WAS patients, including 18 boys with severe classical WAS and 6 boys expressing mild forms of the disease, and then examined the degree of correlation of these as well as all previously published WASP mutations with disease severity. By analysis of these compiled mutation data, we demonstrated clustering of WASP mutations within the four most N-terminal exons of the gene and also identified several sites within this region as hotspots for WASP mutation. These characteristics were observed, however, in both severe and mild cases of the disease. Similarly, while the cumulative data revealed a predominance of missense mutations among the WASP gene lesions observed in boys with isolated thrombocytopenia, missense mutations were not exclusively associated with milder WAS phenotypes, but also comprised a substantial portion (38%) of the WASP gene defects found in patients with severe disease. These findings, as well as the detection of identical WASP mutations in patients with disparate phenotypes, reveal a lack of phenotype concordance with genotype in WAS and thus imply that phenotypic outcome in this disease cannot be reliably predicted solely on the basis of WASP genotypes.

Child↗