ABCMdb

PMID: 8865181

Deltas CC, Boteva K, Georgiou A, Papageorgiou E, Georgiou C
Description of a symptomless cystic fibrosis L346P/M348K compound heterozygous Cypriot individual.
Mol Cell Probes. 1996 Aug;10(4):315-8., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Met348Lys ABCC7 p.Leu346Pro Molecular and Cellular Probes (1996) 10, 315-318 Short Communication Description of a symptomless cystic fibrosis L346P/ M348K compound heterozygous Cypriot individual C. Constantinou Deltas,1 * Kalina Boteva,1 Andreas Georgiou,2 Elena Papageorgiou1 and Christina Georgiou3 1 The Cyprus Institute of Neurology and Genetics, 2 Nicosia General Hospital, and 3 Archbishop Makarios III Hospital, Nicosia, Cyprus (Received 12 January, Accepted 6 February 1996) During the past few years we have been testing the hypothesis that Cyprus may have been spared many severe cystic fibrosis (CF) cases but not cystic fibrosis transmembrane conductance regulator (CFTR) mutations. Login to comment 2 ABCC7 p.Leu346Pro With this approach we identified a mutation, L346P, which in association with the severe mutation F508 or 1677delTA, confers a mild and atypical presentation. Login to comment 3 ABCC7 p.Met348Lys ABCC7 p.Leu346Pro Recently, we identified another entirely symptomless 48-year-old individual, with genotype L346P/M348K. Login to comment 4 ABCC7 p.Met348Lys ABCC7 p.Leu346Pro The fact that M348K was initially identified in a severely affected Italian patient strengthens the hypothesis that L346P, a putative mild mutation, is dominant over severe ones. Login to comment 5 ABCC7 p.Met348Lys One other explanation is that M348K is not a causative defect but a rare polymorphism. Login to comment 17 ABCC7 p.Leu346Pro The second mutation in the three Cypriot patients who carry L346P is F508,is that Cyprus might have been spared many severe CF cases, but not CFTR mutations. Login to comment 18 ABCC7 p.Met348Lys 1677delTA and M348K. Login to comment 24 ABCC7 p.Met348Lys ABCC7 p.Met348Lys Both nonsense and missense mutations have been reportedthat substituted lysine for methionine (M348K). Login to comment 34 ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro pothesis that suggests that severe mutations are recessive over mild mutations.8,10,13 In the three CypriotOur patient (III-7, see Fig. 1) had inherited the M348K mutation from his mother who belongs to a patients, the same L346P mutation, which is present in exon 7, in one of the transmembrane domains offamily of nine siblings. Login to comment 37 ABCC7 p.Met348Lys ABCC7 p.Met348Lys It is associated with three dif-dividual II-2, not only inherited the M348K mutation, most probably from her father, but was found to be ferent mutations, reportedly found in severely affected patients. Login to comment 38 ABCC7 p.Arg347Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro Mutation R347P,14 which is right next toa carrier of another mutation, L346P, that she inherited from her mother. Login to comment 39 ABCC7 p.Leu346Pro She passed one of each mutations L346P, was also found to be associated with mild symptomatology. Login to comment 40 ABCC7 p.Met348Lys However, M348K which is just oneto each of her two offspring. Login to comment 42 ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro She aminoacid further, was initially described in a severely affected patient.7 It is quite interesting that the twohas no symptoms whatsoever, and there has never been any suspicion that she might be suffering from patients with genotypes L346P/ F508 and L346P/ 1677delTA did have some symptoms, althougha major inherited disorder. Login to comment 43 ABCC7 p.Met348Lys ABCC7 p.Leu346Pro She is rather short, but her sister II-11 is also short and is only a carrier of one mild,8 whereas the most recent patient with genotype L346P/M348K has almost no symptomatology at themutation. Login to comment 49 ABCC7 p.Leu346Pro Her physical examination and laboratory examinations were nor- Finally, our findings provide further evidence that mutation L346P might be responsible for the mildmal, including one sweat test. Login to comment 50 ABCC7 p.Leu346Pro Mutation L346P was initially identified in two other symptomatology of CF patients who are also carriers of mutations that are known to seriously affect theunrelated Cypriot patients. Login to comment 52 ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Met348Lys ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro However, onemajor findings other than failure to thrive, occasional electrolyte disturbances and some chest infections in other likely explanation for the symptomless status of the 48-year-old lady described in this report is thatone of the patients.8 So far we are not aware of additional patients from other populations carrying mutation M348K does not really affect the function L346P/M348K CF symptomless individual 317 293 255 38 118 17 NlaIII NlaIII1 428 Abolished by the M348K mutation L346P M348K [M348K/N] L346P/N M348K/N M348K/N M348K/N M348K/N N/N N/N 1 2 3 4 5 6 7 8 9 10 11 12 1 2 1 2 3 4 5 6 7 M348K/NM348K/N L346P/N N/N M348K/? Login to comment 54 ABCC7 p.Met348Lys M348K/L356P N/N I II III I-2 II-2 III-1 III-2 II-5 III-3 II-6 II-7 II-9 II-10 II-11 II-12 III-6 III-7 I-2 II-2 II-2 III-1 III-2 II-5 III-3 II-6 II-7 II-9 II-10 II-11 II-12 III-7 Fig. 1. Login to comment 56 ABCC7 p.Met348Lys ABCC7 p.Leu346Pro The proband was individual III-7, and his maternal aunt II-2 was found to have inherited mutations M348K and L346P. Login to comment 58 ABCC7 p.Leu346Pro L346P was tested by DNA amplification of exon 7, followed by digestion with BstUI. Login to comment 59 ABCC7 p.Met348Lys In the presence of the mutation, the 428 bp DNA product is cleaved to fragments of 266 bp and 162 bp.8 M348K was tested by amplification of exon 7 and digestion with NIaIII. Login to comment