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

Clémence Vanlerberghe 1 Florence Petit 2 Valérie Malan 3 Catherine Vincent-Delorme 2 Sonia Bouquillon 1 Odile Boute 2 Muriel Holder-Espinasse 2, 4 Bruno Delobel 5 Bénédicte Duban 5 Louis Vallée 6 Jean-Marie Cuisset 6 Marie-Pierre Lemaitre 6 Marie-Christine Vantyghem 7 Marie Pigeyre 7 Sandrine Lanco-Dosen 8 Ghislaine Plessis 9 Marion Gérard 9 Matthieu Decamp 9 Michèle Mathieu 10 Gilles Morin 10 Guillaume Jedraszak 10 Frederic Bilan 11 Brigitte Gilbert-Dussardier 12 Delphine Fauvert 13 Joelle Roume 13 Valérie Cormier-Daire 14 Roseline Caumes 14 Jacques Puechberty 15 David Genevieve 15, 16 Pierre Sarda 15, 17 Lucie Pinson 15 Patricia Blanchet 15 Nathalie Lemeur 18 Frenny Sheth Sylvie Manouvrier-Hanu 2 Joris Andrieux 1
Abstract : Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.
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Soumis le : mardi 21 mai 2019 - 14:26:14
Dernière modification le : jeudi 25 juillet 2019 - 14:24:50

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Clémence Vanlerberghe, Florence Petit, Valérie Malan, Catherine Vincent-Delorme, Sonia Bouquillon, et al.. 15q11.2 microdeletion (BP1–BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients. European Journal of Medical Genetics, Elsevier, 2015, 58 (3), pp.140-147. ⟨10.1016/j.ejmg.2015.01.002⟩. ⟨hal-02135606⟩

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