Two novel and correlated CF-causing insertions in the (TG)mTn tract of the CFTR gene

Autoři: Silvia Pierandrei aff001;  Giovanna Blaconà aff002;  Benedetta Fabrizzi aff003;  Giuseppe Cimino aff004;  Natalia Cirilli aff003;  Nicole Caporelli aff003;  Antonio Angeloni aff002;  Marco Cipolli aff003;  Marco Lucarelli aff002
Působiště autorů: Dept. of Mother-Child and Urologic Sciences, Sapienza University of Rome, Rome, Italy aff001;  Dept. of Experimental Medicine, Sapienza University of Rome, Rome, Italy aff002;  Cystic Fibrosis Care Center, Mother - Child Department, United Hospitals, Ancona, Italy aff003;  Cystic Fibrosis Care Center, Umberto I Hospital, Rome, Italy aff004;  Pasteur Institute Cenci Bolognetti Foundation, Rome, Italy aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222838


Two novel and related pathogenic variants of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene were structurally and functionally characterized. These alterations have not been previously described in literature. Two patients with diagnosis of Cystic Fibrosis (CF) based on the presence of one mutated allele, p.Phe508del, pathological sweat test and clinical symptoms were studied. To complete the genotypes of both patients, an extensive genetic and functional analysis of the CFTR gene was performed. Extensive genetic characterization confirmed the presence of p.Phe508del pathogenic variant and revealed, in both patients, the presence of an insertion of part of intron 10 in intron 9 of the CFTR gene, within the (TG)m repeat, with a variable poly-T stretch. The molecular lesions resulted to be very similar in both patients, with only a difference in the number of T in the poly-T stretch. The functional characterization at RNA level revealed a complete anomalous splicing, without exon 10, from the allele with the insertion of both patients. Consequently, the alleles with the insertions are expected not to contribute to the formation of a functional CFTR protein. Molecular and functional features of these alterations are compatible with the definition of novel CF-causing variants of the CFTR gene. This also allowed the completion of the genetic characterization of both patients.

Klíčová slova:

Alleles – Cystic fibrosis – Human genetics – Chlorides – Introns – Nucleotide sequencing – Polymerase chain reaction – Sweat


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