Document Detail


Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances.
MedLine Citation:
PMID:  19328872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Behavioural differences have been described in patients with type I deletions (between breakpoints 1 and 3 (BP1-BP3)) or type II deletions (between breakpoints 2 and 3) of the 15q11.2 Prader-Willi/Angelman region. The larger type I deletions appear to coincide with more severe behavioural problems (autism, ADHD, obsessive-compulsive disorder). The non-imprinted chromosomal segment between breakpoints 1 and 2 involves four highly conserved genes, TUBGCP5, NIPA1, NIPA2, and CYFIP1; the latter three are widely expressed in the central nervous system, while TUBGCP5 is expressed in the subthalamic nuclei. These genes might explain the more severe behavioural problems seen in type I deletions. We describe nine cases with a microdeletion at 15q11.2 between BP1-BP2, thus having a haploinsufficiency for TUBGCP5, NIPA1, NIPA2, and CYFIP1 without Prader-Willi/Angelman syndrome. The clinical significance of a pure BP1-BP2 microdeletion has been debated, however, our patients shared several clinical features, including delayed motor and speech development, dysmorphisms and behavioural problems (ADHD, autism, obsessive-compulsive behaviour). Although the deletion often appeared to be inherited from a normal or mildly affected parent, it was de novo in two cases and we did not find it in 350 healthy unrelated controls. Our results suggest a pathogenic nature for the BP1-BP2 microdeletion and, although there obviously is an incomplete penetrance, they support the existence of a novel microdeletion syndrome in 15q11.2.
Authors:
Marianne Doornbos; Birgit Sikkema-Raddatz; Claudia A L Ruijvenkamp; Trijnie Dijkhuizen; Emilia K Bijlsma; Antoinet C J Gijsbers; Yvonne Hilhorst-Hofstee; Roel Hordijk; Krijn T Verbruggen; W S Mieke Kerstjens-Frederikse; Ton van Essen; Klaas Kok; Anneke T van Silfhout; Martijn Breuning; Conny M A van Ravenswaaij-Arts
Publication Detail:
Type:  Case Reports; Journal Article     Date:  2009-03-27
Journal Detail:
Title:  European journal of medical genetics     Volume:  52     ISSN:  1878-0849     ISO Abbreviation:  Eur J Med Genet     Publication Date:    2009 Mar-Jun
Date Detail:
Created Date:  2009-05-15     Completed Date:  2009-09-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101247089     Medline TA:  Eur J Med Genet     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  108-15     Citation Subset:  IM    
Affiliation:
Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Angelman Syndrome / genetics
Child
Child, Preschool
Chromosome Breakage
Chromosome Deletion*
Chromosome Disorders / genetics*
Chromosomes, Human, Pair 15*
Family Health
Humans
Male
Mental Disorders / genetics*
Prader-Willi Syndrome / genetics*
Speech Disorders
Syndrome

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