Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Moreira, Danielle de Paula; Griesi-Oliveira, Karina; Bossolani-Martins, A.L.; Lourenço, Naila Cristina Vilaça; Takahashi, Vanessa; Rocha, Kátia Maria da; Moreira, Eloísa S.; Vadász, E; Meira, Joanna Goes Castro; Bertola, Débora Romeo; Halloran, Eoghan O’; Magalhães, Tiago R.; Fett‐Conte, Agnes Cristina; Passos‐Bueno, Maria Rita

doi:10.1371/journal.pone.0107705

Cited by 25 publications

(31 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We also found a chromosome 15q13.3 duplication in a child with focal seizures. An association between 15q13.3 duplications and epilepsy has only been reported in a few cases so far . The observations in our cohort suggest that chromosome 15q11.2 and 15q13.3 deletions and duplications might predispose to both generalized and focal epilepsies.…”

Section: Discussionsupporting

confidence: 45%

“…An association between 15q13.3 duplications and epilepsy has only been reported in a few cases so far. 9,21 The observations in our cohort suggest that chromosome 15q11.2 and 15q13.3 deletions and duplications might predispose to both generalized and focal epilepsies. Although these CNVs are regarded as susceptibility CNVs for epilepsy, one should always consider that other causes of epilepsy may also be present, as seen in 30% of the children with susceptibility CNVs in our cohort ( Table 3).…”

Section: Diagnostic Yield Of Microarray Analysismentioning

confidence: 71%

See 1 more Smart Citation

Copy number variation in a hospital‐based cohort of children with epilepsy

et al. 2017

View full text Add to dashboard Cite

SummaryObjectiveTo evaluate the diagnostic yield of microarray analysis in a hospital‐based cohort of children with seizures and to identify novel candidate genes and susceptibility loci for epilepsy.MethodsOf all children who presented with their first seizure in the University Medical Center Groningen (January 2000 through May 2013) (n = 1,368), we included 226 (17%) children who underwent microarray analysis before June 2014. All 226 children had a definite diagnosis of epilepsy. All their copy number variants (CNVs) on chromosomes 1–22 and X that contain protein‐coding genes and have a prevalence of <1% in healthy controls were evaluated for their pathogenicity.ResultsChildren selected for microarray analysis more often had developmental problems (82% vs. 25%, p < 0.001), facial dysmorphisms (49% vs. 8%, p < 0.001), or behavioral problems (41% vs. 13%, p < 0.001) than children who were not selected. We found known clinically relevant CNVs for epilepsy in 24 of the 226 children (11%). Seventeen of these 24 children had been diagnosed with symptomatic focal epilepsy not otherwise specified (71%) and five with West syndrome (21%). Of these 24 children, many had developmental problems (100%), behavioral problems (54%) or facial dysmorphisms (46%). We further identified five novel CNVs comprising four potential candidate genes for epilepsy: MYT1L, UNC5D, SCN4B, and NRXN3.SignificanceThe 11% yield in our hospital‐based cohort underscores the importance of microarray analysis in diagnostic evaluation of children with epilepsy.

show abstract

Section: Discussionsupporting

confidence: 45%

Section: Diagnostic Yield Of Microarray Analysismentioning

confidence: 71%

Copy number variation in a hospital‐based cohort of children with epilepsy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This reinforces that rearrangements in these 2 regions contribute significantly to the phenotype of patients with syndromic SZs. Moreira et al [2014], using the P343 kit, analyzed 531 Brazilian patients with autism. Of these cases, 78 also had SZs.…”

Section: Discussionmentioning

confidence: 99%

“…The authors conclude that changes in 15q13.3 and 22q13 are more prevalent among individuals with autism and epilepsy than in individuals with autism alone. The absence of CNVs in 16p11.2 is explained by the phenotypic variability of patients with changes in this region and by the fact that the overlap between autism and epilepsy is not frequently observed [Moreira et al, 2014].…”

Section: Discussionmentioning

confidence: 99%

Identifying CNVs in 15q11q13 and 16p11.2 of Patients with Seizures Increases the Rates of Detecting Pathogenic Changes

et al. 2016

View full text Add to dashboard Cite

Chromosomal changes are frequently observed in patients with syndromic seizures. Understanding the genetic etiology of this pathology is crucial for the guidance and genetic counseling of families as well as for the establishment of appropriate treatment. A combination of MLPA kits was used to identify pathogenic CNVs in a group of 70 syndromic patients with seizures. Initially, a screening was performed for subtelomeric changes (MLPA P036 and P070 kits) and for the regions most frequently related to microdeletion/microduplication syndromes (MLPA P064). Subsequently, the MLPA P343 was used to identify alterations in the 15q11q13, 16p11.2, and 22q13 regions. Screening with MLPA P343 allowed a 10-15.7% increase in the detection rate of CNVs reinforcing the importance of investigating changes in 15q11q13 and 16p11.2 in syndromic patients with seizures. We also demonstrated that the MLPA technique is an alternative with a great diagnostic potential, and we proposed its use as part of the initial assessment of syndromic patients with seizures.

show abstract

“…No contexto de hotspot, foi identificada no Brasil uma prevalência de CNVs de 2,7% (KUSENDA et al, 2008;SWANWICK et al, 2011;MOREIRA et al, 2014).…”

Section: Caracterização De Cnvs Em Pacientes Com Teaunclassified

InDels e CNVs pequenas em pacientes com Transtorno do Espectro Autista

Silva¹

View full text Add to dashboard Cite

hypothesized that small CNVs (between 1 and 50 Kb), which are below the resolution of most commercial microarrays and and whose detection still has limitations for its detection detection through NGS, could contribute to the phenotype in a proportion of cases. As a first step to address this hypothesis, it was performed the methodology of custom aCGH 60K, covering a total of 269 ASD candidate genes, in order to select potentially pathogenic CNVs among 98Brazilian patients with idiopathic ASD. With this initial screening, the prevalence of potentially pathogenic CNVs obtained was 9%, with 20% of them characterized as small. The subsequent analysis was performed using the 180K custom aCGH methodology, which covered a total of 1527 TEA candidate genes. A total of 63 patients with autism were analyzed with this new array. From these hybridizations, the prevalence of potentially pathogenic CNVs obtained was 12.7%, with 62.5% of them classified as small. This detection rate is quite significant, particularly considering that the sample of patients used was prescreened, in order to exclude patients with the most prevalent CNVs in ASD in the regions 15q11-q13, 16p11.2 and 22q13.3. The last approach used in this work was to compare the detection of CNVs by the methodology of aCGH, gold standard reference for CNVs detection, with the next generation sequencing (NGS).Data from 9 patients obtained by NGS were analyzed using NextGene and XHMM software. The softwares, however, presented discrepant results among themselves and little overlap with the data of aCGH 180K, of 38.9% and 50%, considering NextGene and XHMM respectively. These results suggest that the customized aCGH represents a promising approach for the detection of small CNVs and that these, in turn, can contribute to the risk of ASD in at least 6,3 % of cases.

show abstract

Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Cited by 25 publications

References 83 publications

Copy number variation in a hospital‐based cohort of children with epilepsy

Copy number variation in a hospital‐based cohort of children with epilepsy

Identifying CNVs in 15q11q13 and 16p11.2 of Patients with Seizures Increases the Rates of Detecting Pathogenic Changes

InDels e CNVs pequenas em pacientes com Transtorno do Espectro Autista

Contact Info

Product

Resources

About