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Results for “Codon, Nonsense”

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At least 1,459 records · Page 81Linked to original sources
PubMed1994

Mild beta+(-87)-thalassemia CACCC box mutation is associated with elevated fetal hemoglobin expression in cis.

The beta zero-thalassemia codon 39 nonsense mutation predominant in Sardinia is severe, and homozygotes are transfusion dependent. Two-thirds of beta zero 39 alleles are linked to A gamma T (haplotype II). One-fourth are linked to A gamma I (haplotypes I and IX), as is the mild beta +-thalassemia -87 C-->G mutation (haplotype VIII). beta +/beta zero-Thalassemia VIII/II compound heterozygotes have significantly higher A gamma I:A gamma T (23:7) than beta zero-thalassemia I/II (24:20) or IX/II (16:17) cases. This suggests that the beta + -87 mutation is associated with elevated gamma expression in cis, which may contribute to the lack of transfusion-dependence in beta +/beta zero cases.

Adult↗
PubMedDate not supplied

Beta-globin cluster haplotypes in normal individuals and beta(0)39-thalassemia carriers from Sardinia, Italy.

Seven polymorphic sites in the beta-globin cluster in association with specific thalassemia mutations were analyzed in a sample from Sardinia, Italy. In order to verify previous works carried out on normal samples (beta(A)/beta(A)) and family studies on beta-thalassemia homozygotes individuals, the haplotype frequencies in both normal individuals (beta(A)/beta(A)) and beta(0)39-thalassemia carriers (beta(A)/beta0) were studied. In our work chromosomes carrying beta(0)39 mutation are characterized by a prevalence of haplotype II (- + + - + + +) (52%) relative to haplotype I (+- - - - + +) (29%), in contrast, among chromosomes with beta(A) the frequency of haplotype I is much greater than that of haplotype II. These data confirm what was found by other authors. Nevertheless, our results disagree with those of previous studies of Sardinians, both in frequencies values and in the numbers of haplotypes identified. Population analysis performed with samples carrying the beta-thalassemic mutation highlighted the peculiarity of Sardinians with respect to other Mediterranean populations. The Corsican population is most similar to the Sardinian population, confirming previous analyses performed with both classical markers and mitochondrial and genomic DNA.

Adult↗
PubMed2002

Frameshift mutation in the cartilage-derived morphogenetic protein 1 (CDMP1) gene and severe acromesomelic chondrodysplasia resembling Grebe-type chondrodysplasia.

Grebe-type chondrodysplasia exhibits a severe form of limb shortening and appendicular bone dysmorphogenesis. Here we report a family with seven males and six females who inherited the disorder in an autosomal recessive fashion. While the carrier parents did not exhibit any apparent skeletal abnormalities, all affected patients had a similar phenotype with unaffected axial and craniofacial bones. Since mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene have been reported in similar acromesomelic chondrodysplasias, we examined genomic DNA from affected and normal subjects for possible mutations in CDMP1. In affected subjects, an insertion of a C at nucleotide 297 of the coding sequence was discovered. This insertion produced a shift in the reading frame at amino acid residue 99, causing premature termination of the polypeptide six amino acids downstream. DNA samples from 41 control subjects did not show this mutation. The truncated CDMP1 protein in these subjects is predicted to cause a total loss of its signaling function. The present report confirms that CDMP1 plays an important role in the regulation of axial bone growth during development and suggests that its absence does not impair other developmental processes.

Abnormalities, Multiple↗
PubMed2001

PTEN mutation in a family with Cowden syndrome and autism.

We report on a mother and son with Cowden syndrome and a PTEN mutation. The boy also exhibits autistic behavior and mental retardation, while his mother has a normal intelligence and social interaction pattern. We review the scanty literature data on the association of Cowden syndrome and autism and emphasize that the association of progressive macrocephaly and pervasive developmental disorder seems to be an indication for screening for PTEN mutations.

Autistic Disorder↗
PubMed2003

Effects of MECP2 mutation type, location and X-inactivation in modulating Rett syndrome phenotype.

Rett syndrome (RTT) is a clinically defined disorder that describes a subset of patients with mutations in the X-linked MECP2 gene. However, there is a high degree of variability in the clinical phenotypes produced by mutations in MECP2, even amongst classical RTT patients. In a large-scale screening project, this variability has been examined by looking at the effects of mutation type, functional domain affected and X-inactivation. Mutations have been identified in 60% of RTT patients in this study (25% of whom were atypical), including 23 novel mutations and polymorphisms. More mutations were found in classical patients (63%) compared to atypical patients (44%). All of the pathogenic mutations were de novo in patients for whom parent DNA was available for screening. A composite phenotype score was developed, based on the recommendations for reporting clinical features in RTT of an international collaborative group. This score proved useful for summarising phenotypic severity, but did not correlate with mutation type, domain affected or X-inactivation, probably due to complex interactions between all three. Other correlations suggested that truncating mutations and mutations affecting the methyl-CpG-binding domain tend to lead to a more severe phenotype. Skewed X-inactivation was found in a large proportion (43%) of our patients, particularly in those with truncating mutations and mutations affecting the MBD. It is therefore likely that X-inactivation does modulate the phenotype in RTT.

Australia↗
PubMed2005

Isolated elevated sweat chloride concentrations in the presence of the rare mutation S1455X: an extremely mild form of CFTR dysfunction.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) have been shown to cause typical cystic fibrosis (CF) and several milder phenotypes. We report on two asymptomatic sisters who had isolated increased sweat chloride concentrations, and in whom systematic scanning of the whole coding region of the CFTR gene revealed the F508del/S1455X genotype.

Adult↗
PubMed2005

Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort.

Mutations in the DMD gene result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Readily available clinical tests detect only deletions of one exon or greater, which are found in approximately 60% of cases. Mutational analysis of other types of DMD mutations, such as premature stop codons and small frameshifting insertions or deletions, has historically been hampered by the large size of the gene. We have recently reported a method that allows the rapid and economical sequencing of the entire coding region of the DMD gene, and that is more sensitive than methods based on single-strand conformational polymorphism (SSCP) screening or other preliminary screening steps. Here we use single condition amplification/internal primer (SCAIP) sequencing analysis, in combination with multiplex amplifiable probe hybridization (MAPH) analysis of duplications, to report the frequency of mutations in a large cohort of unselected dystrophinopathy patients from a single clinic. Our results indicate that 7% of dystrophinopathy patients do not have coding region mutations, suggesting that intronic mutations are not uncommon. The availability of rapid and thorough mutation analysis from peripheral blood samples, along with an improved estimate of the percentage of non-coding region mutations, will be of benefit for improved genetic counseling and in identification of cohorts for clinical trials.

Codon, Nonsense↗
PubMed2005

High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss.

Molecular testing for mutations in the gene encoding connexin-26 (GJB2) at the DFNB1 locus has become the standard of care for genetic diagnosis and counseling of autosomal recessive non-syndromic hearing impairment (ARNSHI). The spectrum of mutations in GJB2 varies considerably among the populations, different alleles predominating in different ethnic groups. A cohort of 34 families of Spanish Romani (gypsies) with ARNSHI was screened for mutations in GJB2. We found that DFNB1 deafness accounts for 50% of all ARNSHI in Spanish gypsies. The predominating allele is W24X (79% of the DFNB1 alleles), and 35delG is the second most common allele (17%). An allele-specific PCR test was developed for the detection of the W24X mutation. By using this test, carrier frequencies were determined in two sample groups of gypsies from different Spanish regions (Andalusia and Catalonia), being 4% and 0%, respectively. Haplotype analysis for microsatellite markers closely flanking the GJB2 gene revealed five different haplotypes associated with the W24X mutation, all sharing the same allele from marker D13S141, suggesting that a founder effect for this mutation is responsible for its high prevalence among Spanish gypsies.

Chromosomes, Human, Pair 13↗
PubMed2006

A truncating mutation in the IL1RAPL1 gene is responsible for X-linked mental retardation in the MRX21 family.

X-linked mental retardation (XLMR) is a genetically heterogeneous condition, due to mutations in at least 50 genes, involved in functioning of the central nervous system and located on the X chromosome. Nonspecific XLMR (MRX) is characterized essentially by mental retardation transmitted by X-linked inheritance. More than 80 extended MRX pedigrees have been reported to date, which have been distinguished exclusively by physical position of the corresponding gene on the X chromosome, established by linkage analysis. One such family, MRX21, which was described by us in 1993 and localized to Xp11.4-pter, has now been reanalyzed with additional markers and after one more affected individual had became available. This extra information allowed a significant reduction of the linkage interval and, eventually, identification of the mutant gene. A stop mutation in exon 10 of the IL1RAPL1 gene (in Xp21) was found in the four affected males and in obligate carriers, allowing conclusive counseling of other family members of uncertain carrier status. The W487X mutation results in the production of a truncated IL1RAPL protein, comprised of the extracellular Ig-like domain and transmembrane tract, but lacking the last 210 aminoacids of the cytoplasmic domain. MRX21 is the first extended MRX family with a point mutation in IL1RAPL1 and the second with a stop mutation, which had been previously found only in a small family. Our report confirms the role of the IL1RAPL1 gene in causing nonspecific mental retardation in males and underlines the importance of detailed linkage analysis before candidate gene mutational screening.

Chromosomes, Human, X↗
PubMed2006

Oto-spondylo-megaepiphyseal dysplasia (OSMED): clinical and radiological findings in sibs homozygous for premature stop codon mutation in the COL11A2 gene.

Oto-spondylo-megaepiphyseal dysplasia (OSMED) is a very rare disorder due to mutation of type XI collagen. Less than 30 patients have been reported in the literature so far. It could be either of autosomal dominant (OMIM 154780) or recessive (OMIM 215150) etiology. Two sibs with OSMED are presented. They had disproportionate short stature and short limbs, distinct face with midface hypoplasia, short nose, depressed nasal bridge, long philtrum, and non-progressive sensorineural deafness. Radiological findings showed short long bones and large epiphyses with metaphyseal flaring and mild platyspondyly and coronal clefting. Homozygosity of a single nucleotide deletion in exon 55 causing a premature stop codon in exon 56 of COL11A2 was detected in the affected sibs. Parents were heterozygotes for the same mutation and interestingly, the father had mild unilateral non-progressive sensorineural deafness. This finding adds more weight that the type of mutation and location in COL11A2 are crucial in determining the phenotype. The purpose of this study is to report clinical and radiological findings in two molecularly proven Egyptian sibs with autosomal recessive OSMED.

Base Sequence↗