Testing single/combined clinical categories on 5110 Italian patients with developmental phenotypes to improve array-based detection rate.
Chromosome Aberrations
DNA Copy Number Variations
Developmental Disabilities
/ classification
Genetic Testing
/ methods
Genetics, Medical
/ organization & administration
Humans
Italy
Oligonucleotide Array Sequence Analysis
/ methods
Phenotype
Practice Guidelines as Topic
Sensitivity and Specificity
Societies, Medical
/ standards
Chromosomal microarray analysis (CMA)
clinical marker identification
detection rate
pathogenic CNV
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
25
07
2019
revised:
23
10
2019
accepted:
28
10
2019
pubmed:
19
12
2019
medline:
27
3
2021
entrez:
19
12
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31851782
doi: 10.1002/mgg3.1056
pmc: PMC6978242
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1056Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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