Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes
Martine Doco-Fenzy
(1)
,
Camille Leroy
(1)
,
Anouck Schneider
(2)
,
Florence Petit
(3)
,
Marie-Ange Delrue
(4, 5)
,
Joris Andrieux
(3)
,
Laurence Perrin-Sabourin
(6)
,
Emilie Landais
(1)
,
Azzedine Aboura
(6)
,
Jacques Puechberty
(2, 7)
,
Manon Girard
(7)
,
Magali Tournaire
(7)
,
Elodie Sanchez
(2)
,
Caroline Rooryck
(4, 5)
,
Agnès Ameil
(8)
,
Michel Goossens
(9, 10)
,
Philippe Jonveaux
(11, 12)
,
Geneviève Lefort
(2, 7)
,
Laurence Taine
(4, 5)
,
Dorothée Cailley
(4, 5)
,
Dominique Gaillard
(1)
,
Bruno Leheup
(13, 11)
,
Pierre Sarda
(2)
,
David Genevieve
(2)
1
Service de Génétique
2 Service de génétique médicale [Montpellier]
3 Service de Génétique Médicale [Lille]
4 MRGM - Maladies Rares - Génétique et Métabolisme
5 Service de Génétique Médicale du CHU de Bordeaux
6 Département de génétique [Robert Debré]
7 Plateforme TRANSCRIPTOME
8 American Memorial Hospital (Reims)
9 Laboratoire de génétique moléculaire
10 IMRB - Institut Mondor de Recherche Biomédicale
11 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
12 Service de Génétique [CHRU Nancy]
13 Service de Génétique Clinique Pédiatrique [CHRU Nancy]
2 Service de génétique médicale [Montpellier]
3 Service de Génétique Médicale [Lille]
4 MRGM - Maladies Rares - Génétique et Métabolisme
5 Service de Génétique Médicale du CHU de Bordeaux
6 Département de génétique [Robert Debré]
7 Plateforme TRANSCRIPTOME
8 American Memorial Hospital (Reims)
9 Laboratoire de génétique moléculaire
10 IMRB - Institut Mondor de Recherche Biomédicale
11 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
12 Service de Génétique [CHRU Nancy]
13 Service de Génétique Clinique Pédiatrique [CHRU Nancy]
Martine Doco-Fenzy
- Fonction : Auteur
- PersonId : 1115002
- ORCID : 0000-0001-7429-6201
- IdRef : 075681404
Camille Leroy
- Fonction : Auteur
- PersonId : 20048
- IdHAL : camille-leroy
- ORCID : 0000-0002-6581-377X
Anouck Schneider
- Fonction : Auteur
- PersonId : 765298
- IdRef : 06764208X
Philippe Jonveaux
- Fonction : Auteur
- PersonId : 1403396
- IdRef : 059674563
David Genevieve
- Fonction : Auteur
- PersonId : 907874
- ORCID : 0000-0001-6928-6287
- IdRef : 068913532
Résumé
Obesity is a common but highly, clinically, and genetically heterogeneous disease. Deletion of the terminal region of the short arm of chromosome 2 is rare and has been reported in about 13 patients in the literature often associated with a Prader-Willi-like phenotype. We report on five unrelated patients with 2p25 deletion of paternal origin presenting with early-onset obesity, hyperphagia, intellectual deficiency, and behavioural difficulties. Among these patients, three had de novo pure 2pter deletions, one presented with a paternal derivative der(2)t(2;15)(p25.3;q26) with deletion in the 2pter region and the last patient presented with an interstitial 2p25 deletion. The size of the deletions was characterized by SNP array or array-CGH and was confirmed by fluorescence in situ hybridization (FISH) studies. Four patients shared a 2p25.3 deletion with a minimal critical region estimated at 1.97 Mb and encompassing seven genes, namely SH3HYL1, ACP1, TMEMI8, SNTG2, TPO, PXDN, and MYT1L genes. The fifth patient had a smaller interstitial deletion encompassing the TPO, PXDN, and MYT1L genes. Paternal origin of the deletion was determined by genotyping using microsatellite markers. Analysis of the genes encompassed in the deleted region led us to speculate that the ACP1, TMEM18, and/or MYT1L genes might be involved in early-onset obesity. In addition, intellectual deficiency and behavioural troubles can be explained by the heterozygous loss of the SNTG2 and MYT1L genes. Finally, we discuss the parent-of-origin of the deletion.