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


Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurogenetic disorders caused by the loss of function of imprinted genes in 15q11–q13. The maternally expressed UBE3A gene is affected in AS. Four protein-encoding genes (MKRN3, MAGEL2, NDN and SNURF-SNRPN) and several small nucleolar (sno) RNA genes (HBII-13, HBII-436, HBII-85, HBII-438AHBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear. To examine the role of the HBII-52 snoRNA genes, we have reinvestigated an AS family with a submicroscopic deletion spanning UBE3A and flanking sequences. By fine mapping of the centromeric deletion breakpoint in this family, we have found that the deletion affects all of the 47 HBII-52 genes. Since the complete loss of the HBII-52 genes in family members who carry the deletion on their paternal chromosome is not associated with an obvious clinical phenotype, we conclude that HBII-52 snoRNA genes do not play a major role in PWS. However, we cannot exclude the possibility that the loss of HBII-52 has a phenotypic effect when accompanied by the loss of function of other genes in 15q11–q13.

This is a preview of subscription content, log in to check access.

Fig. 1


  1. Bürger J, Horn D, Tonnies H, Neitzel H, Reis A (2002) Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman syndrome but not Prader–Willi syndrome. Am J Med Genet 111:233–237

    Article  PubMed  Google Scholar 

  2. Cavaillé J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, Bachellerie JP, Brosius J, Hüttenhofer A (2000) Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc Natl Acad Sci USA 97:14311–14316

    Article  PubMed  Google Scholar 

  3. Gallagher RC, Pils B, Albalwi M, Francke U. (2002) Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader–Willi syndrome. Am J Hum Genet 71:669–678

    Article  CAS  PubMed  Google Scholar 

  4. Greger V, Woolf E, Lalande M (1993) Cloning of the breakpoints of a submicroscopic deletion in an Angelman syndrome patient. Hum Mol Genet 2:921–924

    CAS  PubMed  Google Scholar 

  5. Hamabe J, Kuroki Y, Imaizumi K, Sugimoto T, Fukushima Y, Yamaguchi A, Izumikawa Y, Niikawa N. (1991) DNA deletion and its parental origin in Angelman syndrome patients. Am J Med Genet 41:64–68

    Google Scholar 

  6. Heisler LK, Chu HM, Tecott LH. (1998) Epilepsy and obesity in serotonin 5-HT2C receptor mutant mice. Ann N Y Acad Sci 861:74–78

    CAS  PubMed  Google Scholar 

  7. Runte M, Hüttenhofer A, Groß S, Kiefmann M, Horsthemke B, Buiting K (2001) The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum Mol Genet 10:2687–2700

    Article  CAS  PubMed  Google Scholar 

Download references


We thank Dr. Gabriele Gillessen-Kaesbach and Dr. Alexander Hüttenhofer for helpful discussions. Part of this work was supported by the Deutsche Forschungsgemeinschaft (grant BU-907/1-2).

Author information



Corresponding author

Correspondence to Karin Buiting.

Additional information

Electronic Database Information: accession numbers and URLs for data presented herein are as follows: for PAR-4 (accession number AF019617), deletion junction fragment (L15422): GenBank, http://www.ncbi.nlm.nih.gov/Genbank/; for Angelman syndrome [MIM105830]: Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Runte, M., Varon, R., Horn, D. et al. Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader–Willi syndrome. Hum Genet 116, 228–230 (2005). https://doi.org/10.1007/s00439-004-1219-2

Download citation


  • Angelman Syndrome
  • Deletion Breakpoint
  • Paternal Chromosome
  • snoRNA Gene
  • Maternal Chromosome