Types of array findings detectable in cytogenetic diagnosis: a proposal for a generic classification

Srebniak, Malgorzata I.; Diderich, Karin E. M.; Govaerts, L.; Joosten, Marieke; Riedijk, Sam; Galjaard, R. J. H.; Opstal, Diane Van

doi:10.1038/ejhg.2013.254

Cited by 37 publications

(43 citation statements)

References 25 publications

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“…Of these only the pathogenic ones are routinely reported to clinical geneticists and gynecologists. For the purpose of this study all pathogenic array results of 1033 fetuses were reviewed and subclassified in the previously proposed categories: 15 CAUs, unexpected diagnoses (UD) and susceptibility locus (SL) for neurodevelopmental disorders. A special category of pathogenic findings is formed by the incidental findings (IF) in parental samples that were discovered 'by accident' during quality control of the array profiles.…”

Section: Array Findings Classificationmentioning

confidence: 99%

“…15 The frequency is dependent on the technique that has been used. In our cohort large chromosome aberrations were incidentally found during the quality control of the parental array profiles.…”

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

“…SL for neurodevelopmental disorders SL for neurodevelopmental phenotypes may be classified as pathogenic submicroscopic array findings in spite of their variable phenotypes and inheritance from (usually apparently) normal parents. 15,31,32 It is well-established that the incidence of such CNVs among affected individuals is increased in comparison with the general population. Since these disorders of extreme phenotypic heterogeneity and/or of variable expressivity probably depend on the presence of one or more second-site variants to cause a disease, [33][34][35] they should be classified as a separate category of findings even if they seem to match the indication.…”

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

“…Since these disorders of extreme phenotypic heterogeneity and/or of variable expressivity probably depend on the presence of one or more second-site variants to cause a disease, [33][34][35] they should be classified as a separate category of findings even if they seem to match the indication. 15 Moreover, at least some of the SL may modify abnormal phenotypes caused by well-known microdeletions/duplications resulting in more severe phenotypes than expected on the basis of the microdeletion/microduplication alone. 34 Although there are already many cases of SL published, prenatal disclosure is still controversial because of the unquantifiable risks and unpredictable phenotypes after birth.…”

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

“…To study this hypothesis and evaluate the diagnostic value of genomic array we reviewed all cases of fetal ultrasound anomalies tested with single-nucleotide polymorphism (SNP) array in our laboratory and we reclassified the pathogenic array findings as we suggested before. 15 This study presents not only the prevalence of pathogenic array findings in fetuses with ultrasound anomalies but also the nature of the genetic abnormalities found. To our best knowledge this is the first report presenting the contribution of causative array findings (CAUs), UD and SL for neurodevelopmental disorders to the total amount of pathogenic array findings in a large prenatal cohort tested by a single laboratory and with the same array platform.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

et al. 2015

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To evaluate the diagnostic value of single-nucleotide polymorphism (SNP) array testing in 1033 fetuses with ultrasound anomalies we investigated the prevalence and genetic nature of pathogenic findings. We reclassified all pathogenic findings into three categories: causative findings; unexpected diagnoses (UD); and susceptibility loci (SL) for neurodevelopmental disorders. After exclusion of trisomy 13, 18, 21, sex-chromosomal aneuploidy and triploidies, in 76/1033 (7.4%) fetuses a pathogenic chromosome abnormality was detected by genomic SNP array: in 19/1033 cases (1.8%) a microscopically detectable abnormality was found and in 57/1033 (5.5%) fetuses a pathogenic submicroscopic chromosome abnormality was detected. 58% (n = 44) of all these pathogenic chromosome abnormalities involved a causative finding, 35% (n = 27) a SL for neurodevelopmental disorder, and 6% (n = 5) a UD of an early-onset untreatable disease. In 0.3% of parental samples an incidental pathogenic finding was encountered. Our results confirm that a genomic array should be the preferred first-tier technique in fetuses with ultrasound anomalies. All UDs involved early-onset diseases, which is beneficial for the patients to know. It also seems that UDs occur at a comparable frequency among microscopic and submicroscopic pathogenic findings. SL were more often detected than in pregnancies without ultrasound anomalies.

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Section: Array Findings Classificationmentioning

confidence: 99%

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

Section: Rarity Of Particular Imbalances and Postnatal Biasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

et al. 2015

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The first de novo non‐mosaic 14q11.2q13.1 tetrasomy of paternal origin

Tomaszewska

Behrendt

Boter

et al. 2016

American J of Med Genetics Pt A

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Tetrasomy 14q11q13 is a very rare chromosome aberration. So far, only five patients with such an imbalance were described. All these patients had a de novo marker chromosome idic(14)(q13) leading to a partial tetrasomy of chromosome 14. We report on the first case of a de novo non-mosaic partial tetrasomy 14q resulted not from a marker chromosome, but from an inverted triplication on paternal chromosome 14, characterized by using FISH and SNP array. Our patient showed some anomalies described in tetrasomy 14q11q13 with striking presence of paternal UPD(14) features (blepharophimosis, small thorax, and joint contractures, developmental delay). This unique patient supports the hypothesis that 14q11q13 may contain imprinted gene(s) that contribute to the paternal UPD(14) features of joint contractures and/or blepharophimosis. This patient demonstrates the utility of parent of origin testing in patients with de novo chromosome 14 aberrations. Overdosage of 14q11.1q13.1 may cause some features related to UPD(14) phenotype.

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Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies

et al. 2015

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We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5-Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age- or screening-related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early-onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early-onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late-onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication.

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Types of array findings detectable in cytogenetic diagnosis: a proposal for a generic classification

Cited by 37 publications

References 25 publications

Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

Prenatal SNP array testing in 1000 fetuses with ultrasound anomalies: causative, unexpected and susceptibility CNVs

The first de novo non‐mosaic 14q11.2q13.1 tetrasomy of paternal origin

Benefits and Burdens of Using a SNP Array in Pregnancies at Increased Risk for the Common Aneuploidies

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