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Results for “Silent Mutation”

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PubMed2006

Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan.

Ion channels play important roles in signal transduction and in the regulation of the ionic composition of intra- and extracellular fluids. Mutations in ion channels have long been thought to be responsible for some forms of hearing loss. Defects in KCNQ4, a voltage-gated potassium channel, are a cause of nonsyndromic sensorineural deafness type 2, an autosomal dominant form of progressive hearing loss. We present data of mutation analysis of KCNQ4 from 185 unrelated Taiwanese probands with nonsyndromic hearing loss. The analysis revealed three novel KCNQ4 mutations and many polymorphisms. The prevalence of KCNQ4 gene mutations in this study was 1.62% (3/185). The mutations include a missense mutation (F182L) and two silent mutations (R216R and T501T). The F182L missense mutation was located in the S3 domain of KCNQ4. The F182 residue of KCNQ4 is highly conserved in KCNQ4 among various species and is less conserved in all members of the KCNQ family. In addition, although R216R is a silent mutation and does not alter the content of amino acid residue, the neural network prediction system revealed that it can potentially create a novel splice donor site during transcription. This mutation might affect the protein structure of KCNQ4 and consequently the normal function of the K+ channel. Our data provide the first comprehensive analysis of the KCNQ4 gene in Taiwanese patients with nonsyndromic deafness.

Adolescent↗

PubMed2005

Molecular analysis of a 444 bp fragment of the bovine leukaemia virus gp51 env gene reveals a high frequency of non-silent point mutations and suggests the presence of two subgroups of BLV in Chile.

With the aim of achieve a better understanding of the epidemiology and distribution of bovine leukaemia virus (BLV) infection in Chile, we assessed the suitability of using DNA isolated from the leukocyte fraction of bulk milk samples to carry out PCR-RFLP and DNA sequence analysis. The env fragment of BLV was successfully amplified from 33 serologically positive bulk milk samples collected from different geographical areas in the south of Chile. Restriction analysis allowed to classify 17 isolates within the Australian subgroup and 16 within the Belgium subgroup. DNA sequence and multiple alignment analysis of eight Chilean isolates showed a significantly higher frequency of single and double nucleotide substitutions. Most of these mutations were non-silent, resulting in changes at the protein level in several important epitopes of gp51. The Chilean sequences and 59 BLV env sequences available at GenBank, were subjected to a phylogenetic analysis, resulting in four different clusters. The groups identified were not related to those previously defined by restriction analysis. Chilean isolates were included in two different clusters and were genetically not related to isolates collected from neighbouring countries. Considering our results we can conclude: (i) bulk milk samples are suitable to identify the presence of BLV allowing epidemiological and genetic studies to be conducted on large geographical areas; (ii) at least four different genetic groups of BLV were identified by phylogenetic analysis, with Chilean isolates included in two different sub clusters.

Amino Acid Sequence↗

PubMed2000

Analysis of autoimmune bone marrow by antibody-phage display: somatic mutations and third complementarity-determining region arginines in anti-DNA gamma and kappa V genes.

OBJECTIVE: To examine anti-double-stranded DNA (anti-dsDNA) IgG autoantibodies from the bone marrow of individuals with systemic lupus erythematosus (SLE). METHODS: A library of single-chain variable fragments (scFv) was constructed from SLE bone marrow complementary DNA of gamma, kappa, and lambda isotype by cloning into the pHENIX phagemid vector. The library was screened with dsDNA in solution, and 2 anti-DNA phage, DNA1 and DNA4, were isolated and their Ig V genes sequenced. Soluble scFv corresponding to DNA1 and DNA4, and their heavy (H)- and light (L)-chain recombinants, were prepared, purified, and analyzed for binding to DNA by enzyme-linked immunosorbent assay. RESULTS: DNA1 and DNA4 used different Ig H-chain (3-30 and 5-51, respectively) and L-chain (DPK15 and DPK22, respectively) V genes. The ratios of replacement mutations to silent mutations in DNA1 and DNA4 suggest that their V genes were selected for improved antigen binding in vivo. The recombinant between DNA4VH and DNA1VL showed the highest relative affinity for both single-stranded DNA and dsDNA. These 2 Ig subunits contained third complementarity-determining region arginines and had acquired the majority of replacement mutations. CONCLUSION: Anti-dsDNA IgG autoantibodies from the bone marrow of SLE patients exploit diverse V genes and cationic V-D-J and V-J junctions for DNA binding, and accumulate replacement mutations that enhance binding.

Adult↗

PubMed2003

AML1/RUNX1 mutations are infrequent, but related to AML-M0, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies.

AML1/RUNX1, located on chromosome band 21q22, is one of the most important hematopoietic transcription factors. AML1 is frequently affected in leukemia and myelodysplastic syndrome with 21q22 translocations. Recently, AML1 mutations were found in adult hematologic malignancies, especially acute myeloid leukemia (AML)-M0 or leukemia with acquired trisomy 21, and familial platelet disorder with a predisposition toward AML. Through the use of polymerase chain reaction-single-strand conformation polymorphism analysis, we examined the AML1 gene for mutations in 241 patients with pediatric hematologic malignancies, and we detected AML1 mutations in seven patients (2.9%). Deletion was found in one patient, and point mutations in four patients, including three missense mutations, two silent mutations, and one mutation within an intron resulting in an abnormal splice acceptor site. All of the mutations except for one were heterozygous. Mutations within the runt domain were found in six of seven patients. Six of seven patients with AML1 mutations were diagnosed with AML, and one had acute lymphoblastic leukemia. In three of these seven patients, AML evolved from other hematologic disorders. AML1 mutations were found in two of four AML-M0 and two of three patients with acquired trisomy 21. Patients with AML1 mutations tended to be older children. Three of four patients with AML1 mutations who received stem cell transplantation (SCT) are alive, whereas the remaining three patients with mutations without SCT died. These results suggest that AML1 mutations in pediatric hematologic malignancies are infrequent, but are possibly related to AML-M0, acquired trisomy 21, and leukemic transformation. These patients may have a poor clinical outcome.

Adolescent↗

PubMed2003

Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in advanced gastric carcinomas.

A novel tumor suppressor gene, PTEN/MMAC1, located on chromosome band 10q23.3, encodes a 403-amino acid, dual-specificity protein phosphatase. The defects in this gene are responsible for the development of some advanced cancers. Inactivating alterations, including mutations and deletions, in the PTEN/MMAC1 gene have been identified in several types of human cancers and cancer cell lines. To clarify the participation of the PTEN/MMAC1 gene in advanced gastric carcinogenesis, we screened their frequency of mutations in primary advanced gastric adenocarcinoma tissues. Cancer specimens and their corresponding normal tissues were obtained surgically from 60 patients with pathologically proven advanced gastric carcinoma at the Department of Surgery of Kaohsiung Medical University Hospital. All nine exons of the PTEN/MMAC1 gene were amplified using polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis and followed by direct sequencing. After neutral polyacrylamide gel electrophoresis, 17 patients (28.3%) showed an apparent electrophoretic mobility shift between the cancer and its paired normal tissue. These results from direct sequencing indicated that mutations consisted of eight cases (47.1%) of missense mutation, five silent mutations (29.4%), two nonsense mutations (11.8%), a 12-bp deletion (5.9%), and a mutation within the splice donor site of intron 6 (5.9%). The mutation hot spots at codons 45, 66, 82 and 204 in advanced gastric cancer have not been observed previously. Based on the present analysis, our study implicated that the mutations of the PTEN/MMAC1 gene do not occur at a significant rate in human advanced gastric carcinoma, but the rare clustered mutation site (exons 2-6) perhaps suggested that PTEN/MMAC1 might contribute to the gastric carcinogenesis and its progression.

Adenocarcinoma↗

PubMed2002

Phenotypic and genotypic features of Alport syndrome in Chinese children.

Chinese Alport syndrome (AS) was analyzed in 44 unrelated patients who were screened for mutations in the COL4A5 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis or PCR direct sequencing in 30 of the 44 patients. The clinical data showed that all patients had hematuria; 25 of 29 male patients (86%) and 9 of 15 female patients (60%) had proteinuria; 11 of 29 male patients (38%) and 1 of 15 female patients (7%) had nephrotic-level proteinuria; 10 of 21 male patients examined (48%) and 1 of 12 female patients examined (8%) had hearing abnormalities. Renal function remained normal despite hearing abnormalities, and ocular lesions occurred in 10%. Among 30 of 44 patients who had a family history of end-stage renal disease (ESRD), 80% (24/30) belonged to X-linked juvenile kindreds, and 20% (6/30) patients to adult kindreds. Of the 44 patients, 14 did not have a family history of ESRD, while 11 of 14 patients diagnosed with X-linked AS did. DNA analysis revealed four missense mutations, two silent mutations, one substitution, and one in-frame deletion. PCR along with Southern hybridization analysis revealed a large deletion of the paired COL4A5 and COL4A6 genes. Chinese AS patients were characterized clinically with hematuria, heavy proteinuria, and more juvenile forms. Mutations in these patients were usually small mutations, while a large deletion involving the 5' part of both COL4A5 and COL4A6 genes was identified.

Adolescent↗

PubMed1985

Sequence of the viral replicase gene from foot-and-mouth disease virus C1-Santa Pau (C-S8).

The nucleotide sequence of the region including the viral replicase gene, the carboxy terminus of protein P18, and the 3'-extracistronic region of foot-and-mouth disease virus (FMDV) type C1-Santa Pau (C-S8) has been determined from previously cloned cDNA fragments [Villanueva et al., Gene 23 (1983) 185-194]. The comparison with the corresponding gene segments of FMDV of serotypes A or O shows base substitutions in 7.2-8.6% of residues in the replicase gene with no insertions or deletions. This is about fourfold lower variation than found for the region encoding capsid protein VP1 of the corresponding viruses. Intermediate variability (substitution at 16.1-23.6% positions) exists in the 3'-extracistronic region, including point mutations, insertions and deletions. The predicted amino acid sequence of the replicase gene indicates that 75.5-82.6% of mutations are silent and that 93.4% of amino acids are conserved in the four FMDV replicases. The frequency of certain types of silent mutations and of rare codon usage is significantly lower for the replicase gene than for the protein VP1 coding region.

Amino Acid Sequence↗

PubMed2004

Positive selection of synonymous mutations in vesicular stomatitis virus.

Prevailing evolutionary forces are typically deduced from the pattern of differences in synonymous and non-synonymous mutations, under the assumption of neutrality in the absence of amino acid change. We determined the complete sequence of ten vesicular stomatitis virus populations evolving under positive selection. A significant number of the mutations occurred independently in two or more strains, a process known as parallel evolution, and a substantial fraction of the parallel mutations were silent. Parallel evolution was also identified in non-coding regions. These results indicate that silent mutations can significantly contribute to adaptation in RNA viruses, and relative frequencies of synonymous and non-synonymous substitutions may not be useful to resolve their evolutionary history.

Animals↗

PubMed2006

Neuronal tissue-specific ribonucleoprotein complex formation on SOD1 mRNA: alterations by ALS SOD1 mutations.

Amyotrophic lateral sclerosis (ALS) is a fatal disease of unknown etiology. Mutations in copper/zinc superoxide dismutase (SOD1) are the most commonly associated genetic abnormality. Given that SOD1 is ubiquitously expressed, the exclusive vulnerability of motor neurons is one of the most puzzling issues in ALS research. We here report that wild-type SOD1 mRNA forms ribonucleoprotein (RNP) complexes with protein homogenates of neuronal tissue but not with homogenates of non-neuronal tissues. 3' Untranslated region of SOD1 mRNA-dependent RNP complexes functioned to stabilize SOD1 mRNA. Moreover, SOD1 mRNAs harboring ALS-associated mutations, including silent mutations, were deficient in forming RNP complexes. In contrast, SOD1 mRNAs harboring artificial mutations, not known to be associated with ALS, demonstrated preserved RNP complex formation. This paper reports RNP complex formation on SOD1 mRNA as a neuronal tissue-specific and ALS-associated mutation sensitive feature.

Humans↗

PubMed1999

Novel somatic mutations in the VHL gene in Swedish archived sporadic renal cell carcinomas.

Frequent loss-of-function somatic mutations of the VHL gene have been detected in sporadic renal cell carcinoma (RCC), indicating that inactivation of the VHL gene plays a critical role in RCC. In this study, we collected 35 archived Swedish sporadic RCCs identified from an epidemiological study on occupational exposure and kidney cancer to test how well stored pathological specimens could be retrieved and analyzed for VHL mutations. Thirty specimens were successfully analyzed with PCR-SSCP and sequencing. Aberrant SSCP bands were detected in 16 out of the 30 samples (53%). Sequencing analysis of the aberrant bands revealed seven deletions, one insertion, one base substitution on a splicing site, six missense mutations, one silent mutation and several base substitutions in the 5' non-coding region and intron 1. Most were novel somatic mutations that have not been reported in sporadic RCC. The mutations were found in three types of non-papillary RCC cases, i.e. 14 clear cells, one granular chromophilic and one sarcomatoid RCC. Interesting multiple mutations were found in three cases (5, 3, 2 mutations, respectively).

Adult↗

PubMed2002

The hairless gene in androgenetic alopecia: results of a systematic mutation screening and a family-based association approach.

BACKGROUND: Genetic disposition and androgen dependence are important characteristics of the common patterned loss of scalp hair known as androgenetic alopecia (AGA). The genetic factors contributing to AGA are currently unknown. The human hairless gene (HR) has recently been cloned and mutations have been reported in families with autosomal recessive universal congenital alopecia and papular atrichia. The main feature of these disorders is persistent complete absence of hair at or shortly after birth. This suggests that HR is essential and specific for the development of hair. OBJECTIVES: To test the hypothesis that HR may be involved in AGA. METHODS: We systematically screened HR for genetic variability by means of single-strand conformation analysis (SSCA) in 46 unrelated men with AGA. To test for an involvement of HR in the development of AGA, seven common variants were genotyped in 61 families with 93 affected offspring. The results were analysed with the transmission/disequilibrium test (TDT). RESULTS: SSCA showed 15 single nucleotide substitutions: eight missense mutations, four silent mutations and three mutations in exon-flanking intronic sequences. TDT results showed a marginally significant association between AGA and variants 3379-29G/T (P = 0.024) and 2611-68C/T (P = 0.047). These results, however, did not remain significant after applying the conservative Bonferroni correction for multiple testing. CONCLUSIONS: Our results do not provide evidence for a strong involvement of HR in the development of AGA, although a minor role cannot be fully excluded.

Adult↗

PubMed2006

Mutations in the calcium-sensing receptor: a new genetic risk factor for chronic pancreatitis?

OBJECTIVE: In 2003 we identified a family with familial hypocalciuric hypercalcemia (FHH) (heterozygous CASR gene mutation L173P) and a mutation in the pancreatic secretory trypsin inhibitor gene (SPINK1) (N34S). While family members with an isolated calcium-sensing receptor gene (CASR) mutation remained healthy, a combination of the CASR and SPINK1 gene mutation caused chronic pancreatitis (CP). We thus speculate that the combination of two genetic defects affecting calcium homeostasis and pancreatic enzyme activation might represent a novel approach in chronic inherited pancreatic disease. We therefore sought to explore whether CASR gene mutations were prevalent in a cohort of patients with CP and confirmed SPINK1 mutations. MATERIAL AND METHODS: A cohort of 19 families (n=170) with a history of idiopathic CP (ICP) was screened for mutations within the CASR gene; 104 members of that cohort had a mutation (N34S) within the SPINK1 gene and 66 of those were suffering from CP. The entire CASR gene was screened for single strand conformation polymorphism under varying polyacrylamide gel conditions and subjected to direct dideoxy nucleotide sequencing of amplified cDNA. RESULTS: Single-strand conformation polymorphisms were observed in 59 samples, clustering of exons 3, 4 and 7. DNA sequence analysis revealed a yet unreported missense mutation in exon 7 (R896H) and two conservative mutations in exon 4 (F391F) and exon 7 (E790E). Furthermore, an intronic polymorphism in nucleotide position 493-19 G>A was detected in 19 out of 170 members of that cohort. CONCLUSIONS: We identified three novel calcium-sensing receptor gene mutations (1 missense mutation, 2 silent mutations and 1 intronic polymorphism) in a cohort of 19 families with ICP. In particular, the kindred with the R896H mutation presenting with a similar pedigree to the family described above may indicate a role for CASR gene mutations in SPINK1-related CP. Again, only the patient with the combination of both CASR and N34S SPINK1 gene mutation developed pancreatitis, whereas in the healthy parents and children only an isolated CASR or N34S SPINK1 gene mutation could be detected. We suggest that the CASR gene is a novel yet undetected co-factor in a multifactorial genetic setting of SPINK1-related pancreatitis that alters the susceptibility for pancreatitis in these patients.

Calcium Signaling↗

PubMed2001

Understanding human disease mutations through the use of interspecific genetic variation.

Data on replacement mutations in genes of disease patients exist in a variety of online resources. In addition, genome sequencing projects and individual gene sequencing efforts have led to the identification of disease gene homologs in diverse metazoan species. The availability of these two types of information provides unique opportunities to investigate factors that are important in the development of genetically based disease by contrasting long and short-term molecular evolutionary patterns. Therefore, we conducted an analysis of disease-associated human genetic variation for seven disease genes: the cystic fibrosis transmembrane conductance regulator, glucose-6-phosphate dehydrogenase, the neural cell adhesion molecule L1, phenylalanine hydroxylase, paired box 6, the X-linked retinoschisis gene and TSC2/tuberin. Our analyses indicate that disease mutations show definite patterns when examined from an evolutionary perspective. Human replacement mutations resulting in disease are overabundant at amino acid positions most conserved throughout the long-term history of metazoans. In contrast, human polymorphic replacement mutations and silent mutations are randomly distributed across sites with respect to the level of conservation of amino acid sites within genes. Furthermore, disease-causing amino acid changes are of types usually not observed among species. Using Grantham's chemical difference matrix, we find that amino acid changes observed in disease patients are far more radical than the variation found among species and in non-diseased humans. Overall, our results demonstrate the usefulness of evolutionary analyses for understanding patterns of human disease mutations and underscore the biomedical significance of sequence data currently being generated from various model organism genome sequencing projects.

Amino Acids↗

PubMed2006

Evolution and differentiation of MSHR gene in different species.

Coat color offers some prospects for evolutionary studies due to its large amount of presumably adaptive coat color variation and conserved genetic mechanisms of generating different coat colors in different species. Melanocyte-stimulating hormone receptor (MSHR) gene is responsible for intraspecific and interspecific color variation in mammals and birds. A total number of 206 MSHR gene sequences belonging to 84 species, 58 genera, and 20 families were analyzed to investigate its evolution and differentiation in different species. Most of the species have 954 bp and stop codon TGA. Species in Callithrix and Callimico have a stop codon mutation from TGA to TGG and elongate 81 bp with TAG as stop codon. Species in Phasianidae, Fringillidae, and Lemuridae also use TAG as stop codon. The Sus scrofa had an insertion of AACCAGACC encoding Asn-Gln-Thr from 85 to 93 bp. In Bovidae, a brown strain of cow with 966 bp due to the 12-bp duplication of GGCATTGCCCGG from 670 to 681 bp encoding for Gly-Ile-Ala-Arg was found. Teiidae has the smallest number of total mutations (6), silent mutations (3), nonsynonymous mutations (3), average number of nucleotide differences (1.519), synonymous nucleotide diversity (pi(s) = 0.0030), and nonsynonymous nucleotide diversity (pi(a) = 0.0029), and Hominidae, Lemuridae, Canidae, and Teiidae have higher ratio of pi(a)/pi(s) (0.537-0.973). The reconstructed phylogenetic tree of MSHR gene of families is basically consistent with the taxonomy of National Center for Biotechnology Information.

Animals↗

PubMed1998

p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas.

Mutations of the p53 tumor suppressor gene are the most prevalent genetic alteration observed in a wide variety of human cancers. In this study we examined 63 methylcholanthrene (MCA)-induced sarcomas from C57BL/6N x C3H/HeN F1 (BCF1) or C3H/HeN x C57BL/6N F1 (CBF1) mice for p53 gene mutations and loss of heterozygosity (LOH) of chromosome 11. Mutation analysis was done on exons 5 to 8 of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis. This identified 53 potential mutations in 45 sarcomas. Mutations were further confirmed by direct sequencing of the region. Forty-nine of the 53 cases (94%) were missense mutations, while the rest included two nonsense mutations, one silent mutation and one insertional mutation. Spectra of base substitutions were: 25 cases (47%) of G:C-->T:A transversion, 13 cases (25%) of G:C-->A:T transition (CpG site 15%), 13 cases (24%) of G:C-->C:G transversion, a case (2%) of A:T-->T:A transversion and a case (2%) of insertion. In addition, analysis of 5 polymorphic markers of mouse chromosome 11 revealed LOH in ten cases (22%) among those carrying p53 mutations. In nine of these 10 cases, the loss involved all 5 markers. In addition, the loss was biased toward the C57BL allele (9 cases). The present study establishes the pattern of mutation of the p53 gene in MCA-induced mouse sarcomas.

Amino Acid Sequence↗

PubMed2000

The characteristics of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma: comparison between EBV(+) and EBV(-) cases in Japanese population.

We have investigated 114 cases with diffuse large B-cell lymphoma (DLBCL) to clarify the characteristics of DLBCL with Epstein-Barr virus (EBV) infection. Thirteen cases (11.4%) showed EBV-encoded RNA 1 (EBER1) signals by RNA in situ hybridization. EBV-encoded latent membrane protein 1 (LMP1) and EBV-encoded nuclear antigen 2 (EBNA2) were expressed in 11 and 4 cases, respectively. Expression of CD30, Bcl-6 and immunoglobulin (Ig) was found in 92%, 31% and 23% with EBV(+) DLBCL, and in 15%, 79% and 82% with EBV(-) DLBCL, respectively. The sequence of rearranged Ig heavy chain (IgH) variable (V) region gene was analyzed in 5 cases with EBV(+) DLBCL and 61 cases with EBV(-) DLBCL. Somatic mutation was found in all cases except one with EBV(-) DLBCL. Average mutation frequency was 9.6% in EBV(+) DLBCL vs. 11.5% in EBV(-) DLBCL. The rates of replacement mutation vs. silent mutation (R / S values) in complementarity determining region II and framework region III were 2.7 and 1.5 in EBV(+) DLBCL, 2.6 and 1.4 in EBV(-) DLBCL. Crippling mutation generating a stop codon was found in 2 of 5 cases (40%) with EBV(+) DLBCL, but none of 61 cases (0%) with EBV(-) DLBCL. These findings suggest that EBV(+) DLBCL and EBV(-) DLBCL were both derived from germinal center (GC) or post-GC B cells, and EBV(+) DLBCL frequently have a non-functional IgH gene owing to crippling mutation.

Adolescent↗

PubMed2006

Mutational analysis of proapoptotic caspase-9 gene in common human carcinomas.

Mounting evidence indicates that deregulation of apoptosis is involved in the mechanisms of cancer development. Caspase-9 plays a crucial role in the initiation phase of the intrinsic apoptosis pathway. To explore the possibility that the genetic alterations of caspase-9 might be involved in the development of human cancers, we analyzed the entire coding region and all splice sites of the human caspase-9 gene for the detection of somatic mutations in a series of 353 cancers, including 180 gastric, 104 colorectal and 69 lung adenocarcinomas. Overall, we detected three somatic mutations of caspase-9, but all of the mutations were silent mutations. The mutations were observed in 2 of 104 colorectal carcinomas and 1 of 180 gastric carcinomas. These data indicate that the caspase-9 gene is rarely mutated in gastric, colorectal and lung adenocarcinomas, and suggest that caspase-9 gene mutation may not contribute to the pathogenesis of these cancers.

Adenocarcinoma↗

PubMed1998

Screening of the Fc epsilon RI-beta-gene in a Swiss population of asthmatic children: no association with E237G and identification of new sequence variations.

BACKGROUND: The gene of the beta subunit of the high affinity receptor for IgE (Fc epsilon RI-beta) encoded on chromosome 11q13 has recently been identified as a candidate gene for asthma and atopy. Two coding variations, E237G and I181L have been described as being associated with asthma and atopy. Our aim was to investigate a Swiss population of atopic and asthmatic children for variations in this gene. METHODS: We screened all 7 exons of the Fc epsilon RI-beta-gene in 224 atopic/asthmatic, 68 relatives and 159 control subjects using exon amplification by PCR and single strand conformation polymorphism (SSCP) analysis followed by fluorescence based DNA sequencing. RESULTS: The sequence variant E237G was found in 3.7% in atopics and in 2.6% in the control population. None of the samples carried the I181L mutation. In addition, we characterised nine novel mutations (1 nonsense mutation, 2 missense mutations, mutation, 2 silent mutations, 4 intronic mutations). CONCLUSIONS: Our results suggest that the E237G does not have a primary effect on the development of atopy and asthma, and thus excludes the Fc epsilon RI-beta locus from being a candidate gene directly involved in these diseases.

Adolescent↗