The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508).
Eitan Kerem,Mary Corey,Batsheva Kerem,Johanna M. Rommens,Danuta Markiewicz,Henry Levison,Lap-Chee Tsui,Peter R. Durie +7 more
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TLDR
The variable clinical course in patients with cystic fibrosis can be attributed at least in part to specific genotypes at the locus of the cystic Fibrosis gene.Abstract:
Background and Methods. Both the clinical manifestations of cystic fibrosis and the genotypes of patients are heterogeneous, but the associations between the two are not known. We therefore studied blood samples from 293 patients with cystic fibrosis for the presence of the most common disease-causing mutation (ΔF508) on chromosome 7 and compared the results with the clinical manifestations of the disease. Results. The prevalence of the ΔF508 allele in the cohort was 71 percent; 52 percent of the patients were homozygous for the mutation, 40 percent were heterozygous, and 8 percent had other, undefined mutations. The patients who were homozygous for the mutation had received a diagnosis of cystic fibrosis at an earlier age and had a greater frequency of pancreatic insufficiency; pancreatic insufficiency was present in 99 percent of the homozygous patients, but in 72 percent of the heterozygous patients and only 36 percent of the patients with other genotypes. The patients with pancreatic insuffic...read more
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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
Sue Richards,Nazneen Aziz,Nazneen Aziz,Sherri J. Bale,David P. Bick,Soma Das,Julie M. Gastier-Foster,Wayne W. Grody,Madhuri Hegde,Elaine Lyon,Elaine B. Spector,Karl V. Voelkerding,Heidi L. Rehm +12 more
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.
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Predicting the Functional Effect of Amino Acid Substitutions and Indels
TL;DR: A new algorithm, PROVEAN (Protein Variation Effect Analyzer), is developed, which provides a generalized approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions, and in-frame insertions and deletions.
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Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.
Philip M. Farrell,Beryl J. Rosenstein,Terry B. White,Frank J. Accurso,Carlo Castellani,Garry R. Cutting,Peter R. Durie,Vicky A. LeGrys,John Massie,Richard B. Parad,Michael J. Rock,Preston W. Campbell +11 more
TL;DR: Advice is provided for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, which involves a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.
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Cystic fibrosis: molecular biology and therapeutic implications.
TL;DR: Several new approaches to drug therapy for cystic fibrosis are now emerging, and the possibility of successful gene therapy by transfer of the normal gene to airway epithelial cells is being vigorously pursued.
References
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Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.
John R. Riordan,Johanna M. Rommens,Batsheva Kerem,Noa Alon,Richard Rozmahel,Zbyszko Grzelczak,Julian Zielenski,Si Lok,Natasa Plavsic,Jia Ling Chou,Mitchell L. Drumm,Michael C. Iannuzzi,Francis S. Collins,Lap-Chee Tsui +13 more
TL;DR: A deletion of three base pairs that results in the omission of a phenylalanine residue at the center of the first predicted nucleotide-binding domain was detected in CF patients.
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Batsheva Kerem,Johanna M. Rommens,Janet A. Buchanan,Danuta Markiewicz,Tara K. Cox,Aravinda Chakravarti,Manuel Buchwald,Lap-Chee Tsui +7 more
TL;DR: Extended haplotype data based on DNA markers closely linked to the putative disease gene locus suggest that the remainder of the cystic fibrosis mutant gene pool consists of multiple, different mutations.
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Identification of the cystic fibrosis gene: Chromosome walking and jumping
Johanna M. Rommens,Michael C. Iannuzzi,Batsheva Kerem,Mitchell L. Drumm,Georg Melmer,Michael Dean,Richard Rozmahel,Jeffery L. Cole,Dara Kennedy,Noriko Hidaka,Martha Zsiga,Manuel Buchwald,John R. Riordan,Lap-Chee Tsui,Francis S. Collins +14 more
TL;DR: Several transcribed sequences and conserved segments were identified in this cloned region and one corresponds to the cystic fibrosis gene and spans approximately 250,000 base pairs of genomic DNA.
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Rapid method for the determination of fat in feces.
TL;DR: By these methods the fat in feces can be measured within 35 to 45 minutes with an error not exceeding 2 per cent.
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Gastrointestinal Manifestations of Cystic Fibrosis: A Review
TL;DR: Internal medicine and pediatrics in the United States now share the complications and consequences of cystic fibrosis.