Evidence map›Paper›PMID 29523172›Full record

ArticleItalian journal of pediatrics2018

Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies.

I Maini, I Ivanovski, O Djuric, S G Caraffi, E Errichiello, M Marinelli, F Franchi, V Bizzarri, S Rosato, M Pollazzon and 7 more

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Article in Italian journal of pediatrics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

I MainiClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
I IvanovskiClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
O DjuricInstitute of Epidemiology, School of Medicine, University of Belgrade, Belgrade, Serbia.
S G CaraffiClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
E ErrichielloDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
M MarinelliLaboratory of Genetics, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
F FranchiLaboratory of Genetics, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
V BizzarriLaboratory of Genetics, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
S RosatoClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
M PollazzonClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
C GelminiClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
M MalacarneDivision of Medical Genetics, Galliera Hospital, Genoa, Italy.
C FuscoChild Neuropsychiatry Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
G GarganoNeonatal Intensive Care Unit (NICU), Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
S BernasconiFormer Director Pediatric Department, University of Parma, Parma, Italy.
O ZuffardiDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
L GaravelliClinical Genetics Unit, Maternal and Child Health Department, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy. livia.garavelli@ausl.re.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSince 2010, array-CGH (aCGH) has been the first-tier test in the diagnostic approach of children with neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA) of unknown origin. Its broad application led to the detection of numerous variants of uncertain clinical significance (VOUS). How to appropriately interpret aCGH results represents a challenge for the clinician.

methodWe present a retrospective study on 293 patients with age range 1 month - 29 years (median 7 years) with NDD and/or MCA and/or dysmorphisms, investigated through aCGH between 2005 and 2016. The aim of the study was to analyze clinical and molecular cytogenetic data in order to identify what elements could be useful to interpret unknown or poorly described aberrations. Comparison of phenotype and cytogenetic characteristics through univariate analysis and multivariate logistic regression was performed.

resultsCopy number variations (CNVs) with a frequency < 1% were detected in 225 patients of the total sample, while 68 patients presented only variants with higher frequency (heterozygous deletions or amplification) and were considered to have negative aCGH. Proved pathogenic CNVs were detected in 70 patients (20.6%). Delayed psychomotor development, intellectual disability, intrauterine growth retardation (IUGR), prematurity, congenital heart disease, cerebral malformations and dysmorphisms correlated to reported pathogenic CNVs. Prematurity, ventricular septal defect and dysmorphisms remained significant predictors of pathogenic CNVs in the multivariate logistic model whereas abnormal EEG and limb dysmorphisms were mainly detected in the group with likely pathogenic VOUS. A flow-chart regarding the care for patients with NDD and/or MCA and/or dysmorphisms and the interpretation of aCGH has been made on the basis of the data inferred from this study and literature.

conclusionOur work contributes to make the investigative process of CNVs more informative and suggests possible directions in aCGH interpretation and phenotype correlation.

Indexed as

DNA Copy Number VariationsAbnormalities, MultipleAdolescentAdultChildChild, PreschoolComparative Genomic HybridizationFaciesFemaleGenetic TestingHeart Septal Defects, VentricularHumansInfantInfant, NewbornInfant, Premature, DiseasesMaleArray-CGHDysmorphismsInterpretationMultiple congenital anomaliesNeurodevelopmental disorders

Identifiers

PMID29523172
PMCPMC5845186

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.