Implementation of chromosomal microarrays in a cohort of patients with intellectual disability at the Argentinean public health system

Espeche, Lucía D.; Solari, Andrea; Mori, María Ángeles; Arenas, Rubén Martín; Palomares, María; Pérez, Myriam; Martínez, Cinthia Fiorela Azabache; Lotersztein, Vanesa; Segovia, Mabel; Armando, Romina; Daín, Liliana; Nevado, Julián; Lapunzina, Pablo; Rozental, Sandra

doi:10.1007/s11033-020-05743-6

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…Among the 93 patients selected for array-CGH (array comparative genomic hybridization) analysis, 89 samples were studied with the ISCA v2 8×60K platform and 4 with ISCA 4×180K (Agilent, Santa Clara, CA, USA) platform, as previously described [ 30 , 31 ]. For the categorization of the CNVs, the American College of Medical Genetic and Genomics (ACMG) and ClinGen technical standards for interpretation and reporting of constitutional CNVs [ 32 ] were followed.…”

Section: Methodsmentioning

confidence: 99%

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Delea

Massara²,

Espeche³

et al. 2022

Genes

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Congenital anomalies (CA) affect 3–5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.06/1000 births. The aim of this study was to identify the genetic causes in Argentinian patients with MCA and isolated CHD. We recruited 366 patients (172 with MCA and 194 with isolated CHD) born between June 2015 and August 2019 at public hospitals. DNA from peripheral blood was obtained from all patients, while karyotyping was performed in patients with MCA. Samples from patients presenting conotruncal CHD or DiGeorge phenotype (n = 137) were studied using MLPA. Ninety-three samples were studied by array-CGH and 18 by targeted or exome next-generation sequencing (NGS). A total of 240 patients were successfully studied using at least one technique. Cytogenetic abnormalities were observed in 13 patients, while 18 had clinically relevant imbalances detected by array-CGH. After MLPA, 26 patients presented 22q11 deletions or duplications and one presented a TBX1 gene deletion. Following NGS analysis, 12 patients presented pathogenic or likely pathogenic genetic variants, five of them, found in KAT6B, SHH, MYH11, MYH7 and EP300 genes, are novel. Using an algorithm that combines molecular techniques with clinical and genetic assessment, we determined the genetic contribution in 27.5% of the analyzed patients.

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Section: Methodsmentioning

confidence: 99%

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Delea

Massara²,

Espeche³

et al. 2022

Genes

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“…Patients were studied with the ISCA v2 8×60K (Agilent, Santa Clara, CA, USA) platform as previously described [16,17]. In some cases, familial samples were analyzed for a full interpretation of the proband's array results.…”

Section: Chromosomal Microarray Analysis (Cma)mentioning

confidence: 99%

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Delea

Massara

Espeche

et al. 2020

The 1st International Electronic Conference on Genes: Theoretical and Applied Genomics

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In this work, we aim to identify the genetic causes of pathogenesis in Argentinean patients with multiple congenital anomalies (MCA) and isolated Congenital Heart Disease (iCHD). We recruited 174 MCA and 194 iCHD patients from 15 public hospitals. Karyotyping was performed for MCA patients, and MLPA for conotruncal CHD or suspected 2q11 Deletion Syndrome (22q11DS). Selected samples were analyzed by array-CGH (Comparative genomic hybridization) (n = 89) and/or Next-Generation Sequencing (NGS) (n = 18). We successfully analyzed 252/368 patients: 14 had cytogenetic abnormalities, 27 had imbalances in 22q11, and 16 had other clinically relevant copy number variations (CNVs). NGS revealed 12 relevant nucleotide variants (five novels). Combining molecular, clinical and genetic evaluations, the diagnostic yield was 26.2%.

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Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities—A Narrative Review

Chen

2023

Children

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Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene–disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.

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Implementation of chromosomal microarrays in a cohort of patients with intellectual disability at the Argentinean public health system

Cited by 3 publications

References 57 publications

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities—A Narrative Review

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