15q11.2 microdeletion (BP1–BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients

Vanlerberghe, Clémence; Petit, Florence; Malan, Valérie; Vincent‐Delorme, Catherine; Bouquillon, Sonia; Boute, Odile; Holder‐Espinasse, Muriel; Delobel, Bruno; Duban, Bénédicte; Vallée, Louis; Cuisset, Jean‐Marie; Lemaître, M.; Vantyghem, Marie-Christine; Pigeyre, Marie; Lanco-Dosen, Sandrine; Plessis, Ghislaine; Gérard, Marion; Décamp, Matthieu; Mathieu, M; Morin, Gilles; Jedraszak, Guillaume; Bilan, Frédéric; Gilbert‐Dussardier, Brigitte; Fauvert, Delphine; Roume, J.; Cormier‐Daire, Valérie; Caumes, Roseline; Puechberty, Jacques; Geneviève, David; Sarda, Pierre; Pinson, Lucie; Blanchet, P.; Meur, Nathalie Le; Sheth, Frenny; Manouvrier‐Hanu, Sylvie; Andrieux, Joris

doi:10.1016/j.ejmg.2015.01.002

Cited by 81 publications

(56 citation statements)

References 46 publications

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“…This CNV was classified as probably pathogenic ( Fig. 2 ; Table 2 ) [Burnside et al, 2011;Vanlerberghe et al, 2015].…”

Section: Resultsmentioning

confidence: 99%

“…Although there are reports that 9-17% of the individuals with 15q11.2 BP1-BP2 microdeletions are carriers of congenital cardiac defects [Cox and Butler, 2015;Vanlerberghe et al, 2015], this number has not yet been defined for the microduplication syndrome in this region. Some reports describe patients with 15q11.2 BP1-BP2 duplication and CHD, including some with coarctation of the aorta [Abdelmoity et al, 2012;Vanlerberghe et al, 2015], the same malformation as the patient in this study.…”

Section: Discussionmentioning

confidence: 99%

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Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

et al. 2017

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Congenital heart disease (CHD) is the most common congenital disorder among live births. When associated with extracardiac abnormalities, it is characterized as a syndromic heart disease (syndromic CHD) and corresponds to 25% of all liveborn infants with a heart defect. The etiology in about 65% of the cases still remains unknown, and in about 35% of the patients, it is associated with genetic factors. In the present study, MLPA and SNP-array techniques were used to investigate a group of 47 patients with syndromic CHD. In total, 16 defects (34%) were identified, of which 12 (25.5%) were classified as pathogenic or probably pathogenic. The most frequent abnormalities were 22q11.2 deletion (22q11.2 deletion syndrome) and 7q11.23 deletion (Williams-Beuren syndrome). We also show that rarer malformations may be associated with syndromic CHD, such as 14q32.33 deletion as well as 17q25.3, 15q11.2 (BP1-BP2), 22q13.31, and 12p13.31 (SLC2A3) duplications. The present study demonstrates that CNVs are important causal factors and should be studied in patients with syndromic CHD. Furthermore, the use of MLPA as a first screening test was appropriate, as this less expensive technology detected 11 of the 12 pathogenic abnormalities (91.6%).

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“…This CNV was classified as probably pathogenic ( Fig. 2 ; Table 2 ) [Burnside et al, 2011;Vanlerberghe et al, 2015].…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

et al. 2017

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“…Proximal deletions in this complex region (breakpoints BP1-BP2) on chromosome 15 are risk factors of modest effect for neurodevelopmental and neuropsychiatric disorders. 34,74–76 A majority are inherited, 74 typically from a parent with milder or no overt phenotypic consequences. With a nonspecific phenotype and prevalence in control populations of up to 1 in 400, 75 15q11.2 deletions are typically categorized as variants of uncertain significance (VUS).…”

Section: Genome-wide Cnv In Chdmentioning

confidence: 99%

The importance of copy number variation in congenital heart disease

Costain

Silversides

2016

npj Genomic Med

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Congenital heart disease (CHD) is the most common class of major malformations in humans. The historical association with large chromosomal abnormalities foreshadowed the role of submicroscopic rare copy number variations (CNVs) as important genetic causes of CHD. Recent studies have provided robust evidence for these structural variants as genome-wide contributors to all forms of CHD, including CHD that appears isolated without extra-cardiac features. Overall, a CNV-related molecular diagnosis can be made in up to one in eight patients with CHD. These include de novo and inherited variants at established (chromosome 22q11.2), emerging (chromosome 1q21.1), and novel loci across the genome. Variable expression of rare CNVs provides support for the notion of a genetic spectrum of CHD that crosses traditional anatomic classification boundaries. Clinical genetic testing using genome-wide technologies (e.g., chromosomal microarray analysis) is increasingly employed in prenatal, paediatric and adult settings. CNV discoveries in CHD have translated to changes to clinical management, prognostication and genetic counselling. The convergence of findings at individual gene and at pathway levels is shedding light on the mechanisms that govern human cardiac morphogenesis. These clinical and research advances are helping to inform whole-genome sequencing, the next logical step in delineating the genetic architecture of CHD.

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“…There are 4 genes, NIPA1, NIPA2, CYFIP1, and TUBGCP5 , between BP1 and BP2. Recently, microdeletions of this 300-kb region (BP1-BP2) were detected as copy number variations in 0.25% of the healthy population [Cafferkey et al, 2014] and seem to be a risk factor for mental retardation, autism, attention-deficit hyperactivity disorder, learning disorder, epilepsy, and minor dysmorphic features, but no consistant form was detected [Cox and Butler, 2015; Vanlerberghe et al, 2015].…”

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confidence: 99%

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

Niida

Sato²,

Ozaki³

et al. 2016

Cytogenet Genome Res

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Less than 1% of the cases with Angelman syndrome (AS) are caused by chromosomal rearrangements. This category of AS is not well defined and may manifest atypical phenotypes. Here, we report a girl with AS due to der(13)t(13;15)(q14.1;q12)mat. SNP array detected the precise deletion/duplication points and the parental origin of the 15q deletion. Multicolor FISH confirmed a balanced translocation t(13;15)(q14.1;q12) in her mother. Her facial appearance showed some features of dup(13)(pter→q14). Also, she lacked the most characteristic and unique behavioral symptoms of AS, i.e., frequent laughter, happy demeanor, and easy excitability. A review of the literature indicated that AS cases caused by chromosomal rearrangements can be classified into 2 major categories and 4 groups. The first category is paternal uniparental disomy 15, which is subdivided into isodisomy by de novo rob(15;15) and heterodisomy caused by paternal translocation. The second category is the deletion of the AS locus due to maternal reciprocal translocation, which is subdivided into 2 groups associated with partial monosomy by 3:1 segregation and partial trisomy by adjacent-2 segregation. Classification into these categories facilitates the understanding of the mechanisms of chromosomal rearrangements and helps in accurate diagnosis and genetic counseling of these rare forms of AS.

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15q11.2 microdeletion (BP1–BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients

Cited by 81 publications

References 46 publications

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test

The importance of copy number variation in congenital heart disease

Angelman Syndrome Caused by Chromosomal Rearrangements: A Case Report of 46,XX,+der(13)t(13;15)(q14.1;q12)mat,-15 with an Atypical Phenotype and Review of the Literature

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