Puce à ADN pour le diagnostic clinique: une étude de 337 patients avec anomalies congénitales et retards de développement ou déficience intellectuelle

Aperçu: G.M.

L'objectif de l'étude était de déterminer le rendement diagnostique et les critères qui pourraient aider à classer et à interpréter les variations de nombre de copies (CNV) détectées par la technique de la puce à ADN (CMA) chez les patients avec anomalies congénitales et développementales, comprenant la dysmorphie, le retard de développement (DD) ou le handicap intellectuel (ID) , les troubles du spectre de l'autisme (TSA) et les anomalies congénitales (CA).

La puce à ADN a été utile pour établir le diagnostic chez une forte proportion de patients. Les critères de classification et d'interprétation des CNV comprennent la taille et le type de la CNV, le mode d'héritage et la corrélation génotype-phénotype. 

Croat Med J. 2017 Jun 14;58(3):231-238.

Chromosomal microarray in clinical diagnosis: a study of 337 patients with congenital anomalies and developmental delays or intellectual disability

Sansović I¹, Ivankov AM, Bobinec A, Kero M, Barišić I.

Author information

1

Ivona Sansović, Department of Medical Genetics and Reproductive Health, Children's Hospital Zagreb, Klaićeva 16, 10000 Zagreb, Croatia, ivonas3010@gmail.com.

Abstract

AIM:

To determine the diagnostic yield and criteria that could help to classify and interpret the copy number variations (CNVs) detected by chromosomal microarray (CMA) technique in patients with congenital and developmental abnormalities including dysmorphia, developmental delay (DD) or intellectual disability (ID), autism spectrum disorders (ASD) and congenital anomalies (CA).

METHOD:

CMA analysis was performed in 337 patients with DD/ID with or without dysmorphism, ASD, and/or CA. In 30 of 337 patients, chromosomal imbalances had previously been detected by classical cytogenetic and molecular cytogenetic methods.

RESULTS:

In 73 of 337 patients, clinically relevant variants were detected and better characterized. Most of them were >1 Mb. Variants of unknown clinical significance (VOUS) were discovered in 35 patients. The most common VOUS size category was <300 kb (40.5%). Deletions and de novo imbalances were more frequent in pathogenic CNV than in VOUS category. CMA had a high diagnostic yield of 43/307, excluding patients previously detected by other methods.

CONCLUSION:

CMA was valuable in establishing the diagnosis in a high proportion of patients. Criteria for classification and interpretation of CNVs include CNV size and type, mode of inheritance, and genotype-phenotype correlation. Agilent ISCA v2 Human Genome 8x60 K oligonucleotide microarray format proved to be reasonable resolution for clinical use, particularly in the regions that are recommended by the International Standard Cytogenomic Array (ISCA) Consortium and associated with well-established syndromes.

PMID:28613040