Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome

Maren Runte, Raymonda Varon, Denise Horn, Bernhard Horsthemeke, Karen Buiting

Institut fur Humangenetik, Universitatsklinikum Essen, Hufelandstrasse 55, 45122, Essen, Germany.

Hum Genet (2005) 116:228-230

Summary by Jamie H. Bassel, D.C., P.C. 

It has been established that both Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) have both neurologic and genetic manifestations as a result of the loss of function of the affected regions 15q11-q13. It is understood that the maternal gene UBE3A experiences a loss of function in AS.  The following four protein-encoded genes on the paternal side of the 15 chromosome (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438-A, HBII-438-B and HBII-52) are expressed exclusively.  It is not known whether these genes are affected in PWS.  This study re-examined the effect of the HBII-52 snoRNA gene by studying an AS family with a small deletion which spanned the UBE3A and adjacent sequence.  It is widely accepted that the chromosome breakage characteristic of certain genetic diseases, occurs in a new form with no predisposition.  To address this question, it was critical to develop a physical mapping tool, which would allow rapid and accurate map AS breakpoints; to search for sequences that could be implicated in the mechanism of chromosome breakage in PWS and whether the loss of HBII-52 has any effect on the outward, physical appearance of the PWS individual when paired with the absence of other genes in the 15q11-q13 locus.   

In a critical review of an earlier Japanese study, a family with three siblings possessing the loss of UBE3A on the maternal chromosome in the 15q11-q13 locus were diagnosed with AS.  However, within the same family, an individual with a deletion on the paternal chromosome were considered healthy.  It was postulated that certain characteristics of the healthy individual, may have been overlooked.  In a later examination of the same family, it was thought that the HBII-52 snoRNA was not critical in the generation of PWS, but what is quite interesting, is that the in the region of HBII-52 there is an area that corresponds to the significant section of the serotonin 2c receptor that may play a role in PWS.   

In a 2002 study, a fluorescence in situ hybridization study (FISH) determined the breakpoints in the region of SNURF-SNRPN which suggested that 47% of the HBII-52 genes were unaltered by the deletion. Since these genes are processed on the paternal side, they may have some involvement in PWS.   This is important because the HBII-52 has an area similar to that found in serotonin receptors and it is widely accepted that the serotonin receptor is involved in body weight control.   

The data collected in the 2002 study and other recent studies conclude that the loss of HBII-52 has not effect on the outward, physical appearance in PWS.    Most of the genetic differences between individuals can be attributed to single nucleotide polymorphisms, or SNPs. Although most occur in noncoding regions of the genome, SNPs within genes can produce destructive effects.    Three SNPs have been located in the SNURF-SNRPN region 63 in front of the HBII-52.  When further examining the family in this study, it was determined that all deletion carriers’ genome includes only one unique coding of the same region 63.   It was further revealed that there were no clinical signs of obesity in any of the family members in this study.  At this point it cannot be determined in the absence HBII-52 along with other genes in the 15q11-q13 region, whether there is any effect on PWS presentation. 

Abstract - click here

edited: 02/09/2012