title: Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes.
abstract: 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.
authors.affiliation: Service de Génétique, Hôpital Maison-Blanche, CHRU, UFR de Médecine, Reims, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Doco-Fenzy
authors.affiliation: Service de Génétique, Hôpital Maison-Blanche, CHRU, UFR de Médecine, Reims, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Leroy
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France.
authors.forename: Anouck
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Service de Génétique, CHU de Lille, Lille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Petit
authors.affiliation: Service de Génétique Médicale, Laboratoire MRGM, (EA 4576), CHRU de Bordeaux, Bordeaux, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.affiliation: Service de Génétique, CHU de Lille, Lille, France.
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.affiliation: Fédération de Génétique, Hopital Robert Debré, APHP Paris, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Perrin-Sabourin
authors.affiliation: Service de Génétique, Hôpital Maison-Blanche, CHRU, UFR de Médecine, Reims, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Landais
authors.affiliation: Fédération de Génétique, Hopital Robert Debré, APHP Paris, Paris, France.
authors.forename: Azzedine
authors.initials: A
authors.lastname: Aboura
authors.affiliation: 1] Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France [2] Plateforme puce à ADN, CHRU Montpellier, Université Montpellier 1, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Puechberty
authors.affiliation: Plateforme puce à ADN, CHRU Montpellier, Université Montpellier 1, Montpellier, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Girard
authors.affiliation: Plateforme puce à ADN, CHRU Montpellier, Université Montpellier 1, Montpellier, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Tournaire
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Service de Génétique Médicale, Laboratoire MRGM, (EA 4576), CHRU de Bordeaux, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.affiliation: Service de Pédiatrie, American Memorial Hospital, CHRU, Reims, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Ameil
authors.affiliation: Laboratoire de Génétique, AP-HP, et INSERM U-841, CHU Henri Mondor, Créteil, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Goossens
authors.affiliation: Service de Génétique, CHRU de Nancy-Brabois, Inserm U954, Université de Lorraine, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Jonveaux
authors.affiliation: 1] Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France [2] Plateforme puce à ADN, CHRU Montpellier, Université Montpellier 1, Montpellier, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Lefort
authors.affiliation: Service de Génétique Médicale, Laboratoire MRGM, (EA 4576), CHRU de Bordeaux, Bordeaux, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Taine
authors.affiliation: Service de Génétique Médicale, Laboratoire MRGM, (EA 4576), CHRU de Bordeaux, Bordeaux, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Cailley
authors.affiliation: Service de Génétique, Hôpital Maison-Blanche, CHRU, UFR de Médecine, Reims, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Gaillard
authors.affiliation: CHU de Nancy, Pole Enfant, Service de génétique clinique, Vandoeuvre les nancy, F-54511, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.affiliation: Département de Génétique Médicale, CHRU Montpellier, Faculté de Médecine de Montpellier-Nimes, Université Montpellier 1, Montpellier, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
mesh_terms: D002648:Child; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011218:Prader-Willi Syndrome / Q000150:complications / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C561020:MYT1L protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; C530715:TMEM18 protein, human; D014157:Transcription Factors; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases