Reinterpretation of Chromosomal Microarrays with Detailed Medical History

Farooqi, Midhat S.; Figueroa, Shirelle; Gotway, Garrett; Wang, Jason; Luu, Hung S.; Park, Jason

doi:10.1016/j.jpeds.2020.03.020

Cited by 4 publications

(6 citation statements)

References 20 publications

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Section: Discussionsupporting

confidence: 93%

“…We found four pathogenic CNVs and two VOUS-likely pathogenic CNVs in six infants, which indicated that 10.2% of the infants had genetic alterations associated with DD and comorbid conditions. This finding was in concordance with the findings of a previous CMA study conducted in infants with DD [11]. Prevalence of cardiac anomaly, autism spectrum disorder, facial dysmorphism, and brain anomaly in pathogenic, VOUS-likely pathogenic CNV groups, and VOUS with no sub-classification versus VOUS-likely benign, benign, and normal CNVs groups.…”

Section: Discussionsupporting

confidence: 92%

“…However, this diagnostic improvement is associated with a significant economic burden to the caregivers [ 9 ]. Nevertheless, Farooqi et al showed that the diagnostic yield of CMAs, with identification of pathogenic CNVs or variants of unknown significance (VOUS)-likely pathogenic, was less than 10% in infants with DD [ 11 ]. This finding highlights the clear need of a better understanding of DD clinical features and its association with CMA data to reduce unnecessary CMA testing.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Clinical Parameters and Chromosomal Microarray Data in Infants with Developmental Delay

Lee

Park

et al. 2020

Healthcare

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Chromosomal microarray (CMA) is considered a first-tier test for genetic analysis as it can be used to examine gene copy number variations (CNVs) throughout the entire genome, with enhanced sensitivity for detecting submicroscopic deletions and duplications. However, its cost can represent a heavy burden. Moreover, the diagnostic yield of CMA in infants with developmental delay (DD) was reported to be less than 10%. Therefore, we aimed to investigate the relationship between CMA results and clinical features and risk factors of DD. The study included 59 infants with DD who were recruited between August 2019 and February 2020 during a visit to the outpatient clinic of a rehabilitation department. We reviewed the clinical records of the infants regarding gender, age, body weight at birth, delivery method, brain imaging data, perinatal history, and parent-related clinical parameters, such as mother and father age at birth. The infants were categorized according to CMA results, and differences in clinical parameters were evaluated. Except for brain anomalies, there was no statistically significant differences between infants who had pathogenic and variants of unknown significance (VOUS)-likely pathogenic CNVs groups compared with those within the VOUS-likely no sub-classification, VOUS-likely benign, benign, and normal CNVs groups. The incidence of brain anomalies was significantly higher within infants with pathogenic and VOUS-likely pathogenic CNVs groups (p < 0.05). Our study suggests that infants with DD who present dysmorphism or brain anomaly may benefit from early CMA analysis, for adequate diagnosis and timely treatment. Further studies are warranted to confirm the relationship between DD clinical parameters and CMA results.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Relationship between Clinical Parameters and Chromosomal Microarray Data in Infants with Developmental Delay

Lee

Park

et al. 2020

Healthcare

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“…12,29 In addition to supporting reanalysis, this data can also help to define the spectrum of phenotypes associated with a specific disease gene. 29 The process of precise and comprehensive collation of phenotypic data has been termed "Deep Phenotyping" 23,57 . This exercise, along with storing information using standard phenotyping terminology, 43,45 allows for the fullest consideration of possible underlying monogenic causes, whether that be in known human disease genes or novel/ putative disease genes in related biological pathways.…”

Section: Additional Information About the Patient And Related Individ...mentioning

confidence: 99%

“…Although less common, improvements in diagnostic yield have also been reported for the reanalysis of sequence data from panels (increase of 7%) 22 and chromosomal microarrays (34% change in classification). 23 There have been calls for reanalysis to be routinely performed for individuals who remain undiagnosed after clinical genomic testing, [24][25][26][27] with the American College of Medical Genetics and Genomics (ACMG) recognizing the importance of reanalysis across multiple publications. 28,29 However, many groups calling for the routine adoption of reanalysis into clinical practice have highlighted the significant challenges that must be addressed.…”

Section: Introductionmentioning

confidence: 99%