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B Gerrard

Publications and source records attributed to B Gerrard.

15 recordsLinked to original sources
PubMed1992

Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis.

OBJECTIVE: Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. DESIGN: We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. SETTING: All the patients presented to a male infertility clinic of a teaching hospital. SUBJECTS: Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. RESULTS: Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P less than .001). Moreover, we have thus far determined that three of these 16 men are compound heterozygotes, one of whom has a mutation not previously described. Analyses continue on patients who have yet to yield a detectable mutation. CONCLUSIONS: Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives.

Adult↗
PubMed1992

Screening for cystic fibrosis mutations in southern France: identification of a frameshift mutation and two missense variations.

In the search for mutations in the cystic fibrosis gene in patients from the Mediterranean area, we have analysed exons 4, 9, 10, 19, and 21 by the single-strand conformation polymorphism (SSCP) technique in 50 patients with at least one non-delta F508 chromosome. Ten samples demonstrated a shifted band, four in exon 19 and six in exon 21. Sequencing of the PCR fragments has led to the identification of three new sequence alterations, two in exon 19 (3737 delA and I1234V), and one in exon 21 (N1303H). We also analysed the frequency of two known intronic polymorphisms in front of exon 19 (C to A change at nucleotide 3601-65) and exon 21 (G to A change at position 4006-200).

Base Sequence↗
PubMed1992

Typing of HLA-DQA1 and DQB1 using DNA single-strand conformation polymorphism.

The technique of single-strand conformation polymorphism (SSCP), which is capable of distinguishing DNA sequence variability, was adapted to the identification of the HLA-DQA1 and DQB1 alleles. Eight DQA1 alleles and 12 DQB1 alleles were distinguished by amplifying the second exon of the genes in the presence of radioactive deoxynucleotide, denaturing the products with heat, and separating the single strands by electrophoresis in nondenaturing gels. For DQA1, it was possible to distinguish the eight alleles with standard bis-acrylamide or with a Hydrolink gel matrix. Twelve DQB1 alleles were identified by a protocol employing a combination of oligohybridization and SSCP using products amplified by specific DQB1 primers.

Alleles↗
PubMed1991

Two frameshift mutations in the cystic fibrosis gene.

Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We have identified in exon 7 two frameshift mutations, one caused by a two-nucleotide insertion and the other caused by a one-nucleotide deletion; these mutations--CF1154insTC and CF1213delT, respectively, are predicted to shift the reading frame of the protein and to introduce UAA(ochre) termination codons at residues 369 and 368.

Adolescent↗
PubMed1990

Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients.

We have identified three different point mutations in the coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Each mutation segregates with the disease in two- or three-generation pedigrees and is not found on the normal chromosome of any documented cystic fibrosis carrier. One of the mutations is found in two independent families that contain at least one individual with a mild course of disease. All of these alterations replace charged amino acids with less polar residues and are found in the putative transmembrane sections of the molecule. The mutated amino acids are found to be conserved in both rodents and amphibians and lie in a region of CFTR that is believed to form a channel in the membrane. Although these alterations are rare, they provide important clues to functionally important regions of the molecule.

Adenosine Triphosphate↗
PubMed1990

A frame-shift mutation in the cystic fibrosis gene.

Cystic fibrosis (CF) is a common recessive lethal genetic disorder, affecting 1 in 1,600 Caucasians. The disease causes defective regulation of chloride-ion transport in exocrine cells. Although in all CF families the disease is linked to a locus on chromosome 7q31, there is clinical heterogeneity in the severity of the disease and the age at which it is diagnosed. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three-nucleotide deletion (delta F508) causing the loss of a phenylalanine residue in the tenth exon of the CFTR gene has been found on 70% of CF chromosomes. We have now characterized a CF family in which neither parent of the affected individual carries the common mutation, and identified a two-nucleotide insertion in the CF allele of the mother. The mutation introduces a termination codon in exon 13 of the CFTR gene at residue 821, and is predicted to result in the production of a severely truncated nonfunctional protein.

Alleles↗
PubMed1990

Approaches to localizing disease genes as applied to cystic fibrosis.

Using chromosome jumping and walking and restriction fragment length polymorphism (RFLP) analysis, we have defined the region which must contain the cystic fibrosis gene. DNA segments spanning approximately 250 kb in the direction of the gene were isolated and used to identify several new polymorphisms informative in cystic fibrosis families. These RFLPs include a highly polymorphic, CA/GT repeat, and a 10 bp insertion uncovered using the polymerase chain reaction. By analyzing a family with a recombination near the gene, we can exclude this region as containing the mutation. Data on the extent of linkage disequilibrium of these markers provides additional information on where the gene is located.

Base Sequence↗
PubMed1989

Isolation of additional polymorphic clones from the cystic fibrosis region, using chromosome jumping from D7S8.

The cystic fibrosis (CF) locus has been located, by both linkage analysis and physical mapping, to a 900-kb region of 7q22-31 flanked by D7S8 (J3.11) and D7S23 (XV-2c). Using a 100-kb general jumping library, we isolated two sequential jump clones, J31 and J29, to one side of the D7S8 region and one jump clone, J32, to the other side of D7S8, so that the total region covered is about 300 kb. Three new RFLPs were detected by J29 and J32. Using PFGE mapping and the three jump clones, we found it possible to orient D7S8 on the chromosome and, by linkage analysis, to further narrow the CF region by 100 kb. The orientation of D7S8 will be useful for directing the isolation of other jump clones toward the CF locus. Though the newly described RFLPs are in considerable linkage disequilibrium with D7S8 polymorphisms, they increase the informativeness of genetic markers in the D7S8 region and should be useful in prenatal diagnosis.

Chromosomes, Human, Pair 7↗
PubMed1988

TMJ dysfunction.

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Humans↗