Aperçu: G.M.
La micro-délétion interstitielle 2p15p16.1 est un syndrome chromosomique rare signalé précédemment chez 33 patients. Il
se caractérise par une déficience intellectuelle, un retard de
développement, des "troubles du spectre de l'autisme", une microcéphalie,
une faible taille, des caractéristiques dysmorphiques et de multiples
défauts d'organes congénitaux. Il est défini comme un syndrome du gène contigu et deux régions critiques ont été proposées , les loci 2p15 et 2p16.1. Néanmoins,
les patients avec délétion des deux régions critiques ont partagé des
caractéristiques similaires du phénotype et la corarélation
génotype-phénotype n'est toujours pas clair.
Les chercheurs examinent
tous les cas publiés et décrivent trois patients supplémentaires, afin
de définir plus précisément la corrélation phénotype-génotype. Ils discutent ensuite de la contribution des gènes inclus dans la suppression du phénotype anormal. les trois nouveaux patients comparativement à des cas précédents ont mis en
évidence que malgré deux régions critiques, la suppression distale à
2p16.1 et la suppression proximale à 2p15 sont associées à des
phénotypes très proches les uns des autres.
Am J Med Genet A. 2017 Jun 1. doi: 10.1002/ajmg.a.38302.
Molecular and clinical delineation of 2p15p16.1 microdeletion syndrome
Lévy J1,2, Coussement A3, Dupont C1, Guimiot F2,4, Baumann C1, Viot G3, Passemard S1,2, Capri Y1, Drunat S1, Verloes A1, Pipiras E1,2,5, Benzacken B1,2,5, Dupont JM3, Tabet AC1,6.
Author information
- 1
- Genetics Department, AP-HP, Robert-Debré University Hospital, Paris, France.
- 2
- INSERM UMR1141, Paris Diderot University, AP-HP, Robert-Debré Hospital, Paris, France.
- 3
- Cytogenetics Laboratory, APHP, Cochin Hospital, Paris Descartes University, Paris, France.
- 4
- Department of Developmental Biology, APHP Robert-Debré hospital, Paris Diderot University, Sorbonne Paris Cité, Paris, France.
- 5
- University Hospital Jean-Verdier, Department of Cytogenetic, Embryology and Histology, Bondy, France.
- 6
- Neuroscience Department, Génétique Humaine et Fonction Cognitive Unit, Pasteur Institute, Paris, France.
Abstract
Interstitial
2p15p16.1 microdeletion is a rare chromosomal syndrome previously
reported in 33 patients. It is characterized by intellectual disability,
developmental delay, autism spectrum disorders, microcephaly, short
stature, dysmorphic features, and multiple congenital organ defects. It
is defined as a contiguous gene syndrome and two critical regions have
been proposed at 2p15 and 2p16.1 loci. Nevertheless, patients with
deletion of both critical regions shared similar features of the
phenotype and the correlation genotype-phenotype is still unclear. We
review all published cases and describe three additional patients, to
define the phenotype-genotype correlation more precisely. We reported on
two patients including the first prenatal case described so far,
carrying a 2p15 deletion affecting two genes: XPO1 and part of USP34.
Both patients shared similar features including facial dysmorphism and
cerebral abnormalities. We considered the genes involved in the deleted
segment to further understand the abnormal phenotype. The third case we
described here was a 4-year-old boy with a heterozygous de novo 427 kb
deletion encompassing BCL11A and PAPOLG at 2p16.1. He displayed speech
delay, autistic traits, and motor stereotypies associated with brain
structure abnormalities. We discuss the contribution of the genes
included in the deletion to the abnormal phenotype. Our three new
patients compared to previous cases, highlighted that despite two
critical regions, both distal deletion at 2p16.1 and proximal deletion
at 2p15 are associated with phenotypes that are very close to each
other. Finally, we also discuss the genetic counseling of this
microdeletion syndrome particularly in the course of prenatal diagnosis.
© 2017 Wiley Periodicals, Inc.
- PMID: 28573701
- DOI: 10.1002/ajmg.a.38302
