Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis

Molecular Genetics & Genomic Medicine

Adamo Pio D'Adamo¹  Agnese Feresin¹  Ilaria Persico¹  Anna Savoia¹  Giorgia Fontana²  Fabio Sirchia²  Marcello Morgutti²  Roberta Bottega²  Sarah Suergiu²  Michela Faleschini²  Martina La Bianca²  Flavio Faletra²  Massimo Maschio²  Karen S. Raraigh³ 

[1] Department of Medical Sciences University of Trieste Trieste Italy;Institute for Maternal and Child Health – IRCCS Burlo Garofolo Trieste Italy;McKusick‐Nathans Institute of Genetic Medicine Johns Hopkins University School of Medicine Baltimore Maryland USA;

关键词: CFTR gene;    complex allele;    cystic fibrosis;    deletion;    molecular diagnosis;   

DOI  :  10.1002/mgg3.1926

来源: DOAJ

【 摘 要 】

Abstract Background Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. Results We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion. Conclusion This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in‐depth molecular CFTR analysis.

【 授权许可】

Unknown