Independent origins of cystic fibrosis mutations R334W, R347P, R1162X, and 3849+10kbC→T provide evidence of mutation recurrence in the CFTR gene

Núria Morral, Roser Llevadot, Teresa Casals, Paolo Gasparini, Milan Macek, Thilo Dörk, Xavier P. Estivill

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Microsatellite analysis of chromosomes carrying particular cystic fibrosis mutations has shown different haplotypes in four cases: R334W, R347P, R1162X, and 38494+10kbC→T. To investigate the possibility of recurrence of these mutations, analysis of intra- and extragenic markers flanking these mutations has been performed. Recurrence is the most plausible explanation, as it becomes necessary to postulate either double recombinations or single recombinations in conjunction with slippage at one or more microsatellite loci, to explain the combination of mutations and microsatellites if the mutations arose only once. Also in support of recurrence, mutations R334W, R347P, R1162X, and 3849+10kbC→T involve CpG dinucleotides, which are known to have an increased mutation rate. Although only 15.7% of point mutations in the coding sequence of CFTR have occurred at CpG dinucleotides, approximately half of these CpG sites have mutated at least once. Specific nucleotide positions of the coding region of CFTR, distinct from CpG sequences, also seem to have a higher mutation rate, and so it is possible that the mutations observed are recurrent. G→A transitions are the most common change found in those positions involved in more than one mutational event in CFTR.

Original languageEnglish
Pages (from-to)890-898
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - Nov 1994
Externally publishedYes


ASJC Scopus subject areas

  • Genetics

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