Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate

Ilaria Catusi, Maria Paola Recalcati, Ilaria Bestetti, Maria Garzo, Chiara Valtorta, Melissa Alfonsi, Alberta Alghisi, Stefania Cappellani, Rosario Casalone, Rossella Caselli, Caterina Ceccarini, Carlo Ceglia, Anna Maria Ciaschini, Domenico Coviello, Francesca Crosti, Annamaria D'Aprile, Antonella Fabretto, Rita Genesio, Marzia Giagnacovo, Paola GranataIlaria Longo, Michela Malacarne, Giuseppina Marseglia, Annamaria Montaldi, Anna Maria Nardone, Chiara Palka, Vanna Pecile, Chiara Pessina, Diana Postorivo, Serena Redaelli, Alessandra Renieri, Chiara Rigon, Fabiola Tiberi, Mariella Tonelli, Nicoletta Villa, Anna Zilio, Daniela Zuccarello, Antonio Novelli, Lidia Larizza, Daniela Giardino

Research output: Contribution to journalArticle

Abstract

Background: Chromosomal microarray analysis (CMA) is nowadays widely used in the diagnostic path of patients with clinical phenotypes. However, there is no ascertained evidence to date on how to assemble single/combined clinical categories of developmental phenotypic findings to improve the array-based detection rate. Methods: The Italian Society of Human Genetics coordinated a retrospective study which included CMA results of 5,110 Italian patients referred to 17 genetics laboratories for variable combined clinical phenotypes. Results: Non-polymorphic copy number variants (CNVs) were identified in 1512 patients (30%) and 615 (32%) present in 552 patients (11%) were classified as pathogenic. CNVs were analysed according to type, size, inheritance pattern, distribution among chromosomes, and association to known syndromes. In addition, the evaluation of the detection rate of clinical subgroups of patients allowed to associate dysmorphisms and/or congenital malformations combined with any other single clinical sign to an increased detection rate, whereas non-syndromic neurodevelopmental signs and non-syndromic congenital malformations to a decreased detection rate. Conclusions: Our retrospective study resulted in confirming the high detection rate of CMA and indicated new clinical markers useful to optimize their inclusion in the diagnostic and rehabilitative path of patients with developmental phenotypes.

Original languageEnglish
Article numbere1056
JournalMolecular Genetics and Genomic Medicine
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • Chromosomal microarray analysis (CMA)
  • clinical marker identification
  • detection rate
  • pathogenic CNV

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate'. Together they form a unique fingerprint.

  • Cite this

    Catusi, I., Recalcati, M. P., Bestetti, I., Garzo, M., Valtorta, C., Alfonsi, M., Alghisi, A., Cappellani, S., Casalone, R., Caselli, R., Ceccarini, C., Ceglia, C., Ciaschini, A. M., Coviello, D., Crosti, F., D'Aprile, A., Fabretto, A., Genesio, R., Giagnacovo, M., ... Giardino, D. (2020). Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate. Molecular Genetics and Genomic Medicine, 8(1), [e1056]. https://doi.org/10.1002/mgg3.1056