Rare partial octosomy and hexasomy of 15q11-q13 associated with intellectual impairment and development delay: report of two cases and review of literature

Li, Haiyu; Du, Juan; Li, Wen; Cheng, Dehua; He, Wen‐Bin; Yi, Duo; Xiong, Bo; Yuan, Shi‐Min; Tu, Chaofeng; Meng, Lanlan; Luo, Aixiang; Lin, Ge; Lu, Guangxiu; Tan, Yue-Qiu

doi:10.1186/s13039-018-0365-5

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…We assume that causes other than pathogenic CNVs underlie ADHD (Kim et al, 2017). Interestingly, developmental (heart, urogenital system, and brain) and growth defects are part of some syndromes that accompany ASD and/or ID, but both were insignificant in their effects on findings of pathogenic CNVs in our patients (Whittington & Holland, 2018; Li et al, 2018; Mulle et al, 2014; Bourgeron, 2016; Schaefer, 2016; Quintela et al, 2017).…”

Section: Discussionmentioning

confidence: 67%

“…Autism spectrum disorders (ASD) and intellectual disabilities (ID) are overlapping genetically conditioned developmental diseases that are frequently accompanied by ADHD, epilepsy, microcephaly, macrocephaly, dysmorphism, developmental defects, and/or growth defects (Whittington & Holland, 2018; Li et al, 2018; Mulle et al, 2014; Bourgeron, 2016; Schaefer, 2016; Quintela et al, 2017). Copy number variants (CNVs) have been identified as one of the possible cause of these diseases (Miller et al, 2010; Battaglia et al, 2013; De la Torre-Ubieta et al, 2016; Schaefer, 2016; Hehir-Kwa et al, 2013; Merikangas et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…ASD and ID are frequently accompanied by ADHD, developmental and growth defects, epilepsy, micro-/macrocephaly, and/or dysmorphism (Whittington & Holland, 2018; Li et al, 2018; Mulle et al, 2014; Bourgeron, 2016; Schaefer, 2016; Quintela et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients

Capkova

Srovnal

et al. 2019

PeerJ

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BackgroundAutism spectrum disorders (ASD) and intellectual disabilities (ID) are heterogeneous and complex developmental diseases with significant genetic backgrounds and overlaps of genetic susceptibility loci. Copy number variants (CNVs) are known to be frequent causes of these impairments. However, the clinical heterogeneity of both disorders causes the diagnostic efficacy of CNV analysis to be modest. This could be resolved by stratifying patients according to their clinical features.AimFirst, we sought to assess the significance of particular clinical features for the detection of pathogenic CNVs in separate groups of ID and ASD patients and determine whether and how these groups differ from each other in the significance of these variables. Second, we aimed to create a statistical model showing how particular clinical features affect the probability of pathogenic CNV findings.MethodWe tested a cohort of 204 patients with ID (N = 90) and ASD (N = 114) for the presence of pathogenic CNVs. We stratified both groups according to their clinical features. Fisher’s exact test was used to determine the significance of these variables for pathogenic CNV findings. Logistic regression was used to create a statistical model of pathogenic CNV findings.ResultsThe frequency of pathogenic CNV was significantly higher in the ID group than in the ASD group: 18 (19.78%) versus 8 (7%) (p < 0.004). Microcephaly showed a significant association with pathogenic findings in ID patients (p < 0.01) according to Fisher’s exact test, whereas epilepsy showed a significant association with pathogenic findings in ASD patients (p < 0.01). The probability of pathogenic CNV findings when epilepsy occurred in ASD patients was more than two times higher than if epilepsy co-occurred with ID (29.6%/14.0%). Facial dysmorphism was a significant variable for detecting pathogenic CNVs in both groups (ID p = 0.05, ASD p = 0.01). However, dysmorphism increased the probability of pathogenic CNV detection in the ID group nearly twofold compared to the ASD group (44.4%/23.7%). The presence of macrocephaly in the ASD group showed a 25% probability of pathogenic CNV findings by logistic regression, but this was insignificant according to Fisher’s exact test. The probability of detecting pathogenic CNVs decreases up to 1% in the absence of dysmorphism, macrocephaly, and epilepsy in the ASD group.ConclusionDysmorphism, microcephaly, and epilepsy increase the probability of pathogenic CNV findings in ID and ASD patients. The significance of each feature as a predictor for pathogenic CNV detection differs depending on whether the patient has only ASD or ID. The probability of pathogenic CNV findings without dysmorphism, macrocephaly, or epilepsy in ASD patients is low. Therefore the efficacy of CNV analysis is limited in these patients.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients

Capkova

Srovnal

et al. 2019

PeerJ

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“…Autism spectrum disorders (ASD) and intellectual disabilities (ID) are overlapping genetically conditioned developmental diseases that are frequently accompanied by ADHD, epilepsy, microcephaly, macrocephaly, dysmorphism, developmental defects, and/or growth defects (Whittington et al, 2018;Li et al, 2018;Mulle et al, 2014, Bourgeron, 2016Schaefer, 2016;Quintela et al, 2017). Copy number variants (CNVs) have been identified as one of the possible cause of these diseases (Miller et al, 2010, Battaglia et al, 2013, de la Torre-Ubieta et al, 2016Schaefer, 2016;Hehir-Kwa et al, 2013;Merikangas et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…ASD and ID are frequently accompanied by ADHD, developmental and growth defects, epilepsy, micro-/macrocephaly, and/or dysmorphism (Whittington et al, 2018;Li et al, 2018;Mulle et al, 2014, Bourgeron, 2016Schaefer, 2016;Quintela et al, 2017).…”

Section: Peerj Reviewing Pdf | (mentioning

confidence: 99%

Peer Review #1 of "Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients (v0.1)"

Pauly

2019

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Background. Autism spectrum disorders (ASD) and intellectual disabilities (ID) are heterogeneous and complex developmental diseases with significant genetic backgrounds and overlaps of genetic susceptibility loci. Copy number variants (CNVs) are known to be frequent causes of these impairments.However, the clinical heterogeneity of both disorders causes the diagnostic efficacy of CNV analysis to be modest. This could be resolved by stratifying patients according to their clinical features.Aim. First, we sought to assess the significance of particular clinical features for the detection of pathogenic CNVs in separate groups of ID and ASD patients and determine whether and how these groups differ from each other in the significance of these variables. Second, we aimed to create a statistical model showing how particular clinical features affect the probability of pathogenic CNV findings.Method. We tested a cohort of 204 patients with ID (N = 90)and ASD (N = 114) for the presence of pathogenic CNVs. We stratified both groups according to their clinical features. Fisher's exact test was used to determine the significance of these variables for pathogenic CNV findings. Logistic regression was used to create a statistical model of pathogenic CNV findings.Results. The frequency of pathogenic CNV was significantly higher in the ID group than in the ASD group -18 (19.78%) versus 8 (7%) (p < 0.004). Microcephaly showed a significant association with pathogenic findings in ID patients (p < 0.01) according to Fisher's exact test, whereas epilepsy showed a significant association with pathogenic findings in ASD patients (p < 0.01). The probability of pathogenic CNV findings when epilepsy occurred in ASD patients was more than two times higher than if epilepsy cooccurred with ID (29.6%/14.0%). Facial dysmorphism was a significant variable for detecting pathogenic CNVs in both groups (ID p = 0.05, ASD p = 0.01). However, dysmorphism increased the probability of pathogenic CNV detection in the ID group nearly twofold compared to the ASD group (44.4%/23.7%). The presence of macrocephaly in the ASD group showed a 25% probability of pathogenic CNV findings by logistic regression, but this was insignificant according to Fisher's exact test. The probability of detecting pathogenic CNVs decreases up to 1% in the absence of dysmorphism, macrocephaly, and epilepsy in the ASD group.

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Prenatal diagnosis of a de novo tetrasomy 15q24.3‐25.3: Case report and literature review

Zhang

et al. 2020

Clinical Laboratory Analysis

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Background Terminal duplication on chromosome 15q is a rare chromosomal variation. Affected individuals show similar features such as growth dysplasia or the development of frontal bossing, body deformities, facial abnormalities, and genitourinary or cardiovascular disorders. However, it is not yet clear whether such 15q repeats lead to identifiable patterns of clinical abnormalities. Therefore, the purpose of this study was to analyze the prenatal diagnostic results and clinical manifestations of a fetus with 15q duplication and to summarize the literature. Methods The case was a fetus at 28 weeks of gestation. The risk of Down syndrome from second‐trimester screening was 1/140. Prenatal ultrasound and amniocentesis were performed, and chromosomal microarray analysis (CMA) was used for genetic analysis. Results The fetus had abnormal clinical features, including intracardiac echogenic focus in the left ventricle, an aberrant right subclavian artery, and growth delay. The fetal chromosomal karyotype was 46,XX,15q?,12q?,21pstk+, and CMA revealed a 10.163 Mb duplication at 15q24.3‐q25.3. The couple chose to terminate the pregnancy after careful consideration. Conclusions The combination and rational application of cytogenetics technology and molecular genetics technology such as CMA will open up the field of clinical application and provide useful genetic counseling for parents of fetuses carrying such chromosomal duplications.

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Rare partial octosomy and hexasomy of 15q11-q13 associated with intellectual impairment and development delay: report of two cases and review of literature

Cited by 11 publications

References 34 publications

Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients

Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients

Peer Review #1 of "Differences in the importance of microcephaly, dysmorphism, and epilepsy in the detection of pathogenic CNVs in ID and ASD patients (v0.1)"

Prenatal diagnosis of a de novo tetrasomy 15q24.3‐25.3: Case report and literature review

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