Exome sequencing and pathway analysis for identification of genetic variability relevant for bronchopulmonary dysplasia (BPD) in preterm newborns: A pilot study

Paola Carrera, Chiara Di Resta, Chiara Volonteri, Emanuela Castiglioni, Silvia Bonfiglio, Dejan Lazarevic, Davide Cittaro, Elia Stupka, Maurizio Ferrari, Marco Somaschini, Rosario Magaldi, Matteo Rinaldi, Gianfranco Maffei, Mauro Stronati, Chryssoula Tzialla, Alessandro Borghesi, Paolo Tagliabue, Tiziana Fedeli, Marco Citterio, Fabio MoscaMariarosa Colnaghi, Anna Lavizzari, Massimo Agosti, Gaia Francescato, Giulia Pomero, Cristina Dalmazzo, Antonio Boldrini, Rosa Scaramuzzo, Enrico Bertino, Silvia Borgione, Claudio Martano, Virgilio Carnielli, Stefano Nobile, Antonietta Auriemma, Cristina Bellan, Giuseppe Carrera, Chiara Zambetti, Riccardo Pucello, Sara Palatta

Research output: Contribution to journalArticlepeer-review


Background: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infancy, affecting preterm children with low birth weight. The disease has a multifactorial aetiology with a significant genetic component; until now published association studies have identified several candidate genes but only few of these data has been replicated. In this pilot study, we approached exome sequencing aimed at identifying non-common variants, which are expected to have a stronger phenotypic effect. Materials and methods: We performed this study on 26 Italian severely affected BPD preterm unrelated newborns, homogeneously selected from a large prospective cohort. We used an Illumina HiSeq 2000 for sequencing. Data analysis was focussed on genes previously associated to BPD susceptibility and to new candidates in related pathways, highlighted by a prioritization analysis performed using ToppGene Suite. Results: By exome sequencing, we identified 3369 novel variants, with a median of 400 variations per sample. The top candidate genes highlighted were NOS2, MMP1, CRP, LBP and the toll-like receptor (. TLR) family. All of them have been confirmed with Sanger sequencing. Conclusions: Potential candidate genes have been discovered in this preliminary study; the pathogenic role of identified variants will need to be confirmed with functional and segregation studies and possibly with further methods, able to evaluate the collective influence of rare variants.Moreover, additional candidates will be tested and genetic analysis will be extended to all affected children.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalClinica Chimica Acta
Publication statusPublished - Oct 15 2014


  • Bronchopulmonary dysplasia
  • Exome sequencing
  • Genetics

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical


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