A novel 5p15.33-14.1 deletion and 4q34.24-35.2 duplication in a patient with mental retardation, dysmorphic features and severe speech delay

Cao, Qinying; Peng, Yuanyuan; Ge, Jun; Zhang, Yanhua; Zhu, Junzhen; Zhao, Luo

doi:10.1007/s12041-014-0318-7

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Positive association between significant CNVs and congenital heart disease in patients with ID/GDD has been reported ( 13 , 36 , 37 ). A chromosomal aberration can contribute to the etiology of speech and language delay ( 38 , 39 ). Fair skin is commonly seen in patients with Prader-Willi syndrome and Angelman syndrome ( 40 , 41 ), and it was also noticed in our patients with these diagnoses.…”

Section: Discussionmentioning

confidence: 99%

Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Kessi

Xiong

et al. 2018

Front. Neurol.

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Introduction: The concurrence of intellectual disability/global developmental delay and epilepsy (ID/GDD-EP) is very common in the pediatric population. The etiologies for both conditions are complex and largely unknown. The predictors of significant copy number variations (CNVs) are known for the cases with ID/GDD, but unknown for those with exclusive ID/GDD-EP. Importantly, the known predictors are largely from the same ethnic group; hence, they lack replication.Purpose: We aimed to determine and investigate the diagnostic yield of CNV tests, new causative CNVs, and the independent predictors of significant CNVs in Chinese children with unexplained ID/GDD-EP.Materials and methods: A total of 100 pediatric patients with unexplained ID/GDD-EP and 1,000 healthy controls were recruited. The American College of Medical Genetics guideline was used to classify the CNVs. Additionally, clinical information was collected and compared between those with significant and non-significant CNVs.Results: Twenty-eight percent of the patients had significant CNVs, 16% had variants of unknown significance, and 56% had non-significant CNVs. In total, 31 CNVs were identified in 28% (28/100) of cases: 25 pathogenic and 6 likely pathogenic. Eighteen known syndromes were diagnosed in 17 cases. Thirteen rare CNVs (8 novel and 5 reported in literature) were identified, of which three spanned dosage-sensitive genes: 19q13.2 deletion (ATP1A3), Xp11.4-p11.3 deletion (CASK), and 6q25.3-q25.3 deletion (ARID1B). By comparing clinical features in patients with significant CNVs against those with non-significant CNVs, a statistically significant association was found between the presence of significant CNVs and speech and language delay for those aged above 2 years and for those with facial malformations, microcephaly, congenital heart disease, fair skin, eye malformations, and mega cisterna magna. Multivariate logistic regression analysis allowed the identification of two independent significant CNV predictors, which are eye malformations and facial malformations.Conclusion: Our study supports the performance of CNV tests in pediatric patients with unexplained ID/GDD-EP, as there is high diagnostic yield, which informs genetic counseling. It adds 13 rare CNVs (8 novel), which can be accountable for both conditions. Moreover, congenital eye and facial malformations are clinical markers that can aid clinicians to understand which patients can benefit from the CNV testing and which will not, thus helping patients to avoid unnecessary and expensive tests.

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Section: Discussionmentioning

confidence: 99%

Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Kessi

Xiong

et al. 2018

Front. Neurol.

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“…O'Neill MJF, http://www.omim.org/entry/605130, accessed 12/11/14). The proband presented distinctive facial features, short stature, hypotonia and developmental delay; mutations and/or copy number variations in a broad variety of genes have been identified in both human and experimental studies to be variably responsible for the above combined features (Cao et al 2014;Pavone et al 2014;Portin 2014;Singh et al 2014). We had therefore not suspected WSS in the proband, and the diagnosis was made only on whole exome sequencing after many other avenues had been explored, including metabolic tests, CGH and mitochondrial DNA sequencing.…”

Section: Resultsmentioning

confidence: 99%

Whole exome sequencing reveals a MLL de novo mutation associated with mild developmental delay and without ‘hairy elbows’: expanding the phenotype of Wiedemann–Steiner syndrome

Steel

Salpietro

Phadke

et al. 2015

J Genet

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A novel 5p15.33-14.1 deletion and 4q34.24-35.2 duplication in a patient with mental retardation, dysmorphic features and severe speech delay

Cited by 2 publications

References 10 publications

Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Rare Copy Number Variations and Predictors in Children With Intellectual Disability and Epilepsy

Whole exome sequencing reveals a MLL de novo mutation associated with mild developmental delay and without ‘hairy elbows’: expanding the phenotype of Wiedemann–Steiner syndrome

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