ABCMdb

PMID: 7527370

Mercier B, Raguenes O, Estivill X, Morral N, Kaplan GC, McClure M, Grebe TA, Kessler D, Pignatti PF, Marigo C, et al.
Complete detection of mutations in cystic fibrosis patients of Native American origin.
Hum Genet. 1994 Dec;94(6):629-32., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCC7 p.Gly542* As the most common mutation found in Caucasians (AF508) was absent and only one chromosome carried the G542X mutation, we decided to analyze the entire coding sequence of the CFTR gene in eight Pueblo CF patients. Login to comment 3 ABCC7 p.Gly542* ABCC7 p.Asp648Val We have identified four different mutations: G542X, Rl162X, 3849+10kbC---~T, and D648V that account for these 16 haplotypes. Login to comment 8 ABCC7 p.Asp648Val A novel mutation, D648V, observed on one chromosome has not been found outside the Pueblo population. Login to comment 18 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The other mutations most frequently found in Caucasians, such as G551D, R553X, N1303K, or W1282X, were also excluded and only one patient was found to carry the G542X. Login to comment 47 ABCC7 p.Gly542* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Arg1162* ABCC7 p.Asp648Val ABCC7 p.Asp648Val First, the change to valine instead of aspartic acid would introduce a conformational change in the R domain, a region of the protein that plays a major Table 1 Clinical and mutations data of these Native American cystic fibrosis (CF) patients Patient Nation Pancreatic Weight Height Haplosufficient (PS) (%ile) (%ile) type Pancreatic insufficient (PI) Mutations 021-l Pueblo PI 20 10 CC Zuni 022-1 Pueblo P1 7.5 20 CC Zuni 023-1 Pueblo PI 75 50 CC Zuni 024-1 Pueblo PI 40 10 CC Zuni 028-1 Pueblo PI 7.7 5 CC Zuni 029-1 Pueblo PS 2 17.5 AC Zuni 006-1 Pueblo PS 8.5 45 AC Jemez 008-1 Pueblo Santo PS > 95 > 95 AB Domingo R1162X R1162X R1162X R1162X R1162X R1162X D648V G542X R1162X R1162X R1162X R1162X R1162X 3849+ 10kbC---~T 3849+ I0kbC----~T 3849+ 10kbC--)T Fig. 1 Sequencing data of the D648V. Login to comment 52 ABCC7 p.Arg1162* This was, in fact, the case as the five patients were shown by DNA sequencing to carry two copies of the R1162X mutation. Login to comment 53 ABCC7 p.Arg1162* Another patient carried the R1162X on only one allele. Login to comment 57 ABCC7 p.Arg1162* To characterize genetic backgrounds associated with R1162X, we used both intra-and extragenic markers. Login to comment 66 ABCC7 p.Gly542* The fourth mutation, G542X, was present on a single chromosome. Login to comment 68 ABCC7 p.Arg1162* First, since the R1162X occurs as a single haplotype in Zuni, all 11 chromosomes could be identical by descent as a result of racial admixture with Spanish or Italian settlers. Login to comment 72 ABCC7 p.Arg553* In the CFTR gene, Reiss et al. (1991) have reported the presence of R553X in both an African-American patient and a German patient. Login to comment 74 ABCC7 p.Arg1162* In this report we have shown that the R1162X mutation is observed on a CpG dinucleotide, resulting in a stop codon. Login to comment