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

  title={Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader–Willi syndrome},
  author={Maren Runte and Raymonda Varon and Denise Horn and Bernhard Horsthemke and Karin Buiting},
  journal={Human Genetics},
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-438A, HBII-438B and HBII-52) are expressed from the paternal chromosome only but their contribution to PWS is unclear. To examine the role of the… Expand
Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader–Willi syndrome mouse models
It is concluded that the lack of Pwcr1/MBII-85 snoRNA expression is the most likely cause for the neonatal lethality in PWS model mice. Expand
A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader–Willi syndrome
It is concluded that a deficiency of MKRN3, MAGEL2 and NDN is not sufficient to cause Prader–Willi syndrome, and two patients with PWS who have an atypical deletion on the paternal chromosome that does not include MKRN 3, MAGel2 andNDN are reported. Expand
Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster
A microdeletion of the HBII-85 snoRNAs in a child with PWS provides, in combination with previous data, effectively conclusive evidence that deficiency of HBOs causes the key characteristics of the PWS phenotype, although some atypical features suggest that other genes in the region may make more subtle phenotypic contributions. Expand
Deletion of the MBII-85 snoRNA Gene Cluster in Mice Results in Postnatal Growth Retardation
This is the first example in a multicellular organism of genetic deletion of a C/D box snoRNA gene resulting in a pronounced phenotype of Prader-Willi syndrome, and it is reported the deletion of PWScr. Expand
Paternally inherited microdeletion at 15q11.2 confirms a significant role for the SNORD116 C/D box snoRNA cluster in Prader–Willi syndrome
Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis and Array CGH testing for genomic copy-number changes in cases with complex phenotypes is proving to be invaluable in detecting novel alterations and enabling better genotype–phenotype correlations. Expand
Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region
An updated version of a sequence-based physical map for a complex chromosomal region is presented, and the possibility of polymorphism in the genomic orientation of the BP1 to BP2 region is raised. Expand
Differential regulation of non-protein coding RNAs from Prader-Willi Syndrome locus
Prader-Willi Syndrome (PWS) is a neurogenetic disorder caused by the deletion of imprinted genes on the paternally inherited human chromosome 15q11-q13. This locus harbours a long non-protein-codingExpand
A deletion of the HBII-85 class of small nucleolar RNAs (snoRNAs) is associated with hyperphagia, obesity and hypogonadism.
Findings provide direct evidence for the role of a particular family of non-coding RNAs, the HBII-85 snoRNA cluster, in human energy homeostasis, growth and reproduction. Expand
Rapid Birth-and-Death Evolution of Imprinted snoRNAs in the Prader-Willi Syndrome Locus: Implications for Neural Development in Euarchontoglires
The data suggest that the regulatory role of HBII-52 on 5-HT2CR pre-mRNA might originate in the Euarchontoglires through adaptive process, and strong selective constraints on the functional elements of these imprinted snoRNAs further suggest that they are subjected to birth-and-death evolution. Expand
A computational screen for C/D box snoRNAs in the human genomic region associated with Prader-Willi and Angelman syndromes.
This computational study employs key motif features of C/D box snoRNAs and introduces a complementary RNA-RNA hybridization test, and identifies three previously unknown methylation guide snoRNA candidates targeting ribosomal 18S and 28S RNAs, and two sno RNAs targeting serotonin receptor 2C mRNA. Expand


Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome.
It is shown that the transcripts reported to be expressed in lymphoblast-somatic cell hybrids are not expressed in fibroblasts, and this hypothesis that loss of expression of the snoRNAs in the proposed minimal critical region confers much or all of the phenotype of PWS is consistent. Expand
Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman syndrome but not Prader-Willi syndrome.
The hypothesis that the functional loss of maternal UBE3A gene activity is sufficient to cause AS is supported and that the deleted region does not contain genes or other structures that are involved in PWS. Expand
The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A.
It is reported here that a processed antisense transcript of UBE3A starts at the IC, and the SNURF-SNRPN sense/UBE3A antisense transcription unit spans more than 460 kb and contains at least 148 exons, including the previously identified IPW exons. Expand
Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization.
Three C/D-box small nucleolar RNAs (snoRNAs) and one H/ACA-box snoRNA in mouse and human are identified, demonstrating their paternal imprinting status and pointing to their potential role in the etiology of PWS. Expand
Cloning of the breakpoints of a submicroscopic deletion in an Angelman syndrome patient.
The results suggest that the imprinted gene(s) responsible for the PWS phenotype are proximal of pB11 in this deletion overlap region. Expand
DNA deletion and its parental origin in Angelman syndrome patients.
Results were consistent with the genomic imprinting hypothesis for the occurrence of AS, i.e., the lack of a maternally derived locus leads to AS, but may not support a model that AS is the alternative phenotype of PWS at the identical locus. Expand
Epilepsy and Obesity in Serotonin 5‐HT2C Receptor Mutant Mice
A role for 5‐HT2C receptors in the serotonergic regulation of body weight and food intake is established andaired‐feeding studies suggest that the obesity syndrome is a result of increased food intake. Expand