Duplication of the 15q11-q13 region: clinical and genetic study of 30 new cases.
BACKGROUND
15q11-q13 region is an area of well-known susceptibility to genomic rearrangements, in which several breakpoints have been identified (BP1-BP5). Duplication of this region is observed in two instances: presence of a supernumerary marker chromosome (SMC) derived of chromosome 15, or interstitial tandem duplication. Duplications are clinically characterized by a variable phenotype that includes central hypotonia, developmental delay, speech delay, seizure, minor dysmorphic features and autism.


METHODS
Retrospective clinical and molecular study of 30 unrelated patients who were identified among the patients seen at the genetic clinics of Robert DEBRE hospital with microduplication of the 15q11-q13 region.


RESULTS
Fifteen patients presented with a supernumerary marker derived from chromosome 15. In fourteen cases the SMC was of large size, encompassing the Prader-Willi/Angelman critical region. All but one was maternal in origin. One patient had a PWS-like phenotype in absence of maternal UPD. In one case, the marker had a smaller size and contained only the BP1-BP2 region. Fifteen patients presented with interstitial duplication. Four cases were inherited from phenotypically normal parents (3 maternal and 1 paternal). Phenotypic features were somewhat variable and 57% presented with autism. Twelve patients showed cerebral anomalies and 18 patients had an abnormal EEG with a typical, recognizable pattern of excessive diffuse rapid spikes in the waking record, similar to the pattern observed after benzodiazepine exposure. Duplication of paternally expressed genes MKRN3, MAGEL2 and NDN in two autistic patients without extra material of a neighboring region enhances their likelihood to be genes related to autism.
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France; Jazan University, Faculty of Medicine, Jazan, Saudi Arabia.
Essam
E
Al Ageeli
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Séverine
S
Drunat
Department of Physiology, AP-HP, Robert Debré Hospital, Paris, France.
Catherine
C
Delanoë
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Laurence
L
Perrin
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Clarisse
C
Baumann
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Yline
Y
Capri
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Jennifer
J
Fabre-Teste
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Azzedine
A
Aboura
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Céline
C
Dupont
Department of Child Neurology, AP-HP, Robert Debré Hospital, Paris, France.
Stéphane
S
Auvin
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Laila
L
El Khattabi
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Dominique
D
Chantereau
Medical Genetic Department, La Timone Hospital, Marseille, France.
Anne
A
Moncla
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France.
Anne-Claude
AC
Tabet
Department of Medical Genetics, APHP -- Robert Debré University Hospital, and Paris VII Denis Diderot University, Paris, France; INSERM UMR676 "PROTECT", Robert Debré Hospital, Paris, France. Electronic address: alain.verloes@rdb.aphp.fr.
Alain
A
Verloes
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D058674:Chromosome Duplication; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D012189:Retrospective Studies; D055815:Young Adult
Autism; Developmental delay; EEG; Parental origin; Seizure; invdup(15)