TY - JOUR
T1 - Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate
AU - Catusi, Ilaria
AU - Recalcati, Maria Paola
AU - Bestetti, Ilaria
AU - Garzo, Maria
AU - Valtorta, Chiara
AU - Alfonsi, Melissa
AU - Alghisi, Alberta
AU - Cappellani, Stefania
AU - Casalone, Rosario
AU - Caselli, Rossella
AU - Ceccarini, Caterina
AU - Ceglia, Carlo
AU - Ciaschini, Anna Maria
AU - Coviello, Domenico
AU - Crosti, Francesca
AU - D'Aprile, Annamaria
AU - Fabretto, Antonella
AU - Genesio, Rita
AU - Giagnacovo, Marzia
AU - Granata, Paola
AU - Longo, Ilaria
AU - Malacarne, Michela
AU - Marseglia, Giuseppina
AU - Montaldi, Annamaria
AU - Nardone, Anna Maria
AU - Palka, Chiara
AU - Pecile, Vanna
AU - Pessina, Chiara
AU - Postorivo, Diana
AU - Redaelli, Serena
AU - Renieri, Alessandra
AU - Rigon, Chiara
AU - Tiberi, Fabiola
AU - Tonelli, Mariella
AU - Villa, Nicoletta
AU - Zilio, Anna
AU - Zuccarello, Daniela
AU - Novelli, Antonio
AU - Larizza, Lidia
AU - Giardino, Daniela
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Chromosomal microarray analysis (CMA)
KW - clinical marker identification
KW - detection rate
KW - pathogenic CNV
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U2 - 10.1002/mgg3.1056
DO - 10.1002/mgg3.1056
M3 - Article
C2 - 31851782
AN - SCOPUS:85076756874
VL - 8
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
SN - 2324-9269
IS - 1
M1 - e1056
ER -