Journal Article

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

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

2020

Overview

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. This study provides a retrospective study coordinated by the Italian Society of Human Genetics (SIGU) of 5,110 patients referred to CMA for variable combined clinical phenotypes, collected by 17 Italian laboratories. The data extrapolated by the present cohort are compared to those of previously reported studies. In addition, the detection rate of single/combined clinical categories of patients sorted out from the overall cohort is evaluated to correctly assess the inclusion of the CMA in the diagnostic path of patients with the developmental clinical phenotypes.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Arrays / Autism / Chromosomal microarray analysis (CMA) / Chromosome Aberrations / Chromosomes / clinical marker identification / Congenital defects / Congenital diseases / Copy number / Cytogenetics / detection rate / Developmental Disabilities - classification / Developmental Disabilities - diagnosis / Developmental Disabilities - genetics / Diagnostic systems / DNA Copy Number Variations / Genetic Testing - methods / Genetic Testing - standards / Genetics / Genetics, Medical - organization & administration / Genomes / Heredity / Humans / Intellectual disabilities / Italy / Laboratories / Oligonucleotide Array Sequence Analysis - methods / Oligonucleotide Array Sequence Analysis - standards / Original / pathogenic CNV / Patients / Phenotype / Phenotypes / Practice Guidelines as Topic / Questionnaires / Sensitivity and Specificity / Societies, Medical - standards / Subgroups