ABCMdb

PMID: 9950364

Padoa C, Goldman A, Jenkins T, Ramsay M
Cystic fibrosis carrier frequencies in populations of African origin.
J Med Genet. 1999 Jan;36(1):41-4., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCC7 p.Asp1270Asn In addition, two out of five black CF patients with positive sweat tests were found to be heterozygous for the 3120+1G→A mutation and two out of another four black patients with symptoms suggestive of CF, but unconfirmed by sweat tests, were heterozygous for the D1270N mutation. Login to comment 7 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr A further three CFTR mutations, A559T, S1255X, and 444delA, which had been found in African-American CF patients, were not identified in the patients or in over 373 healthy subjects tested. Login to comment 15 ABCC7 p.Arg553* ABCC7 p.Ser1255* ABCC7 p.Gly480Cys ABCC7 p.Ala559Thr Together, eight mutations (405+3A→C, 444delA, G480C, R553X, A559T, 2307insA, 3120+1G→A, and S1255X) account for 23.1% of African-American CF chromosomes. Login to comment 24 ABCC7 p.Gly1249Glu ABCC7 p.Gly1249Glu In 1996, three southern African black CF patients with symptoms typical of those seen in white CF patients, that is, pancreatic insuYciency, respiratory infections, and positive sweat tests, were shown to have CFTR mutations.8 The three CFTR mutations identified in the South African black CF patients were 3120+1G→A, G1249E, and 3196del54.8 Of these three CF patients investigated, one was homozygous for the 3120+1G→A mutation and the other two were compound heterozygotes, each with the 3120+1G→A mutation on one chromosome and either the G1249E or the 3196del54 mutation on the other chromosome. Login to comment 27 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr If the mutations that have also been found in the white population were excluded, the 3120+1G→A mutation would account for 53% of African-American CFTR mutations.4 This mutation has also been found in a black CF patient whose father, the 3120+1G→A carrier, is from Cameroon.8 More recently, the mutation has been identified in three Greek families10 and it has also been shown to be a common CFTR mutation (25% of their CF chromosomes) in Saudi Arabia.11 In an attempt to establish how common CF is in African populations, healthy unrelated subjects were screened for four mutations: 3120+1G→A,9 A559T,12 S1255X,13 and 444delA.14 They occur in African-American CF patients at frequencies of 12.2%, 2.0%, 1.4%, and 0.7%, respectively.4 Subjects and methods DNA samples from 208 San and 1152 unrelated, healthy African blacks from southern, western, and central Africa were studied. Login to comment 33 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr DNA was extracted using the salting out method.15 MUTATION DETECTION The healthy subjects and the nine patients with symptoms suggestive of CF were screened for four CFTR mutations (3120+1G→A, A559T, 444delA, and S1255X). Login to comment 35 ABCC7 p.Ser1255* Screening methods for the 444delA and S1255X mutations were previously reported by White et al14 and Cutting et al,13 respectively. Login to comment 36 ABCC7 p.Ala559Thr The A559T mutation creates an MseI site generating fragments of 10, 13, 66, 142, and 194 bp when the mutation is present and 10, 13, 66, and 336 bp fragments in the absence of the mutation. Login to comment 38 ABCC7 p.Gly1249Glu The nine patients were further investigated by SSCP analysis to detect the G1249E mutation (found in the heterozygous state of one of the original three South African black CF patients)8 in exon 20 of the CFTR gene. Login to comment 40 ABCC7 p.Asp1270Asn Sequencing showed the presence of the D1270N mutation, the detection of which was confirmed by a PCR assay. Login to comment 41 ABCC7 p.Asp1270Asn The D1270N mutation destroys a TaqI restriction endonuclease site.16 In the absence of the mutation, fragments of 256 and 217 bp are generated. Login to comment 47 ABCC7 p.Asp1270Asn Results Of the nine black patients with symptoms suggestive of CF, two were heterozygous for the 3120+1G→A mutation (both had positive sweat tests) and two were heterozygous for the D1270N mutation (a sweat test had not been performed in one and was negative in the other). Login to comment 48 ABCC7 p.Asp1270Asn D1270N was detected by SSCP analysis and subsequent sequencing (of the first patient), while the second chromosome carrying this mutation was identified by means of the PCR assay. Login to comment 49 ABCC7 p.Ser1255* ABCC7 p.Gly1249Glu ABCC7 p.Ala559Thr The mutations F508, G1249E, A559T, S1255X, and 444delA were not found in any of the patients. Login to comment 58 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr No heterozygotes were identified in 519, 519, and 373 subjects tested for the A559T, S1255X, and 444delA mutations, respectively. Login to comment 59 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr With a 95% confidence interval, the frequencies of subjects who are carriers for these mutations are low in African populations (0-0.0074 for A559T and S1255X; 0-0.0092 for 444delA)18 and the allele frequencies would be even lower. Login to comment 63 ABCC7 p.Asp1270Asn Of the nine black patients suspected of having CF, two were heterozygous for the 3120+1G→A mutation and two were heterozygous for the D1270N mutation. Login to comment 65 ABCC7 p.Asp1270Asn This mutation seems to be very rare as it has only been reported in 1/2083 CF chromosomes.19 The two patients who are heterozygous for the D1270N mutation may have a milder form of CF as this mutation has been associated with CBAVD and sodium and chloride concentrations in the normal range. Login to comment 75 ABCC7 p.Ser1255* ABCC7 p.Ala559Thr The mutations A559T, S1255X, and 444delA were not found in the unaVected black subjects screened. Login to comment