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Eur J Med Genet. 2015 Mar;58(3):140-7. doi: 10.1016/j.ejmg.2015.01.002. Epub 2015 Jan 14.

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

Author information

1
Institut de génétique médicale, Hôpital Jeanne de Flandre, CHRU Lille, France. Electronic address: clemence.vanlerberghe@chru-lille.fr.
2
Service de génétique clinique, Hôpital Jeanne de Flandre, CHRU Lille, France.
3
Service de cytogénétique et d'embryologie, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
4
Institut de génétique médicale, Hôpital Jeanne de Flandre, CHRU Lille, France.
5
Service de génétique clinique, Hôpital Jeanne de Flandre, CHRU Lille, France; Department of Clinical Genetics, Guy's Hospital, London, UK.
6
Centre de cytogénétique, Hôpital Saint Vincent de Paul, Lille, France.
7
Service de neuropédiatrie, Hôpital Jeanne de Flandre, CHRU Lille, France.
8
Service d'endocrinologie, Hôpital Claude Huriez, CHRU Lille, France.
9
Service de neuropédiatrie, Hôpital de Sambre - Avesnois, Maubeuge, France.
10
Service de génétique clinique, CHU Caen, France.
11
Service de génétique clinique, CHU Amiens, France.
12
Laboratoire de Génétique cellulaire et moléculaire, Pôle Biologie Santé, CHU Poitiers, France.
13
Service de génétique clinique, La Milétrie, CHU Poitiers, France.
14
Service de cytogénétique, CHI Poissy, France.
15
Unité de génétique médicale, CHI Poissy, France.
16
Unité de génétique médicale, Hôpital Necker-Enfants malades, AP-HP, Paris, France.
17
Service de génétique médicale, CHRU Montpellier, France.
18
Service de cytogénétique, CHU Rouen, France.
19
Institute of Human Genetics, Jodhpur Village Road, Gujarat, India.

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.

KEYWORDS:

15q11.2 microdeletion; BP1–BP2; CYFIP1; Congenital heart disease; NIPA1; NIPA2; TUBGCP5

PMID:
25596525
DOI:
10.1016/j.ejmg.2015.01.002
[Indexed for MEDLINE]

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