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)
1
Institut de Génétique Médicale [CHRU Lille]
2 Service de génétique clinique (CHU Lille)
3 Laboratoire Histologie Embryologie Cytogénétique [CHU Necker]
4 Guy's Hospital [London]
5 Hôpital Saint-Vincent de Paul
6 Service de Neuro-pédiatrie[Lille]
7 Hôpital Claude Huriez [Lille]
8 CHR Sambre-Avesnois
9 Service de Génétique [CHU Caen]
10 CHU Amiens-Picardie
11 Service de Génétique Médicale [CHU Poitiers]
12 Laboratoire de génétique clinique [Service de génétique, CHU Poitiers]
13 CHI Poissy-Saint-Germain
14 Service de Génétique Médicale [CHU Necker]
15 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
16 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
17 UM - Université de Montpellier
18 CHU Rouen
2 Service de génétique clinique (CHU Lille)
3 Laboratoire Histologie Embryologie Cytogénétique [CHU Necker]
4 Guy's Hospital [London]
5 Hôpital Saint-Vincent de Paul
6 Service de Neuro-pédiatrie[Lille]
7 Hôpital Claude Huriez [Lille]
8 CHR Sambre-Avesnois
9 Service de Génétique [CHU Caen]
10 CHU Amiens-Picardie
11 Service de Génétique Médicale [CHU Poitiers]
12 Laboratoire de génétique clinique [Service de génétique, CHU Poitiers]
13 CHI Poissy-Saint-Germain
14 Service de Génétique Médicale [CHU Necker]
15 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
16 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
17 UM - Université de Montpellier
18 CHU Rouen
Valérie Malan
- Fonction : Auteur
- PersonId : 975693
Guillaume Jedraszak
- Fonction : Auteur
- PersonId : 1151788
- ORCID : 0000-0002-5704-6830
- IdRef : 181710013
Brigitte Gilbert-Dussardier
- Fonction : Auteur
- PersonId : 1236595
- ORCID : 0000-0001-7182-9914
- IdRef : 081235380
Frenny Sheth
- Fonction : Auteur
Résumé
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.