Home LiteratureArticle Details
PMID: 8845846 Published · ppublish English Case Reports Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.

Human molecular genetics ·Vol. 5 ·No. 4 ·1996-04-00 ·Pages 517-24

Sun Y, Nicholls RD, Butler MG, Saitoh S, Hainline BE, Palmer CG

Abstract

A patient with Prader-Willi syndrome (PWS) was found to carry a de novo balanced reciprocal translocation, t(15;19)(q12;q13.41), which disrupted the small nuclear ribonucleoprotein N (SNRPN) locus. The translocation chromosome 15 was found to be paternal in origin. Uniparental disomy and abnormal DNA methylation were ruled out. The translocation breakpoint was found to have occurred between exon 0 (second exon) and 1 (third exon) of the SNRPN locus outside of the SmN open reading frame (ORF), which is intact. The transcriptional activities of ZNF127, IPW, PAR-1, and PAR-5 were detected with RT-PCR from fibroblasts of the patient, suggesting that these genes may not play a significant role in the PWS phenotype in this patient. Transcription from the first two exons and last seven exons of the SNRPN gene was also detected with RT-PCR; however, the complete mRNA (10 exons) was not detected. Thus, the PWS phenotype in the patient is likely to be the result of disruption of the SNRPN locus.

MeSH Terms
Autoantigens/genetics Base Sequence Blotting, Southern Child, Preschool Chromosomes, Human, Pair 15 Chromosomes, Human, Pair 19 DNA DNA Damage DNA Primers Female Humans In Situ Hybridization, Fluorescence Male Methylation Molecular Sequence Data Pedigree Prader-Willi Syndrome/genetics RNA Ribonucleoproteins, Small Nuclear/genetics Translocation, Genetic snRNP Core Proteins
Chemicals
Autoantigens DNA Primers Ribonucleoproteins, Small Nuclear SNRPN protein, human snRNP Core Proteins RNA DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sun Y
Department of Medical and Molecular Genetics, Indiana University Medical Center, Indianapolis 46202-5251, USA.
Nicholls R D
Butler M G
Saitoh S
Hainline B E
Palmer C G
References (38)
38 references, click to expand
  1. A variety of genetic mechanisms are associated with the Prader-Willi syndrome.
    Am J Med Genet. 1994 Sep 15;54(3):219-26 PMID: 7810579
  2. Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.
    Nat Genet. 1994 Sep;8(1):52-8 PMID: 7987392
  3. Allele-specific replication timing of imprinted gene regions.
    Nature. 1993 Jul 29;364(6436):459-63 PMID: 8332218
  4. Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13.
    Hum Genet. 1992 Nov;90(3):313-5 PMID: 1487250
  5. Identification of a novel paternally expressed gene in the Prader-Willi syndrome region.
    Hum Mol Genet. 1994 Oct;3(10):1877-82 PMID: 7849716
  6. Genomic imprinting.
    Genes Dev. 1988 Aug;2(8):921-5 PMID: 3049238
  7. Parental origin of chromosome 15 deletion in Prader-Willi syndrome.
    Lancet. 1983 Jun 4;1(8336):1285-6 PMID: 6134086
  8. Prader-Willi syndrome: consensus diagnostic criteria.
    Pediatrics. 1993 Feb;91(2):398-402 PMID: 8424017
  9. Sequence-independent amplification and labeling of yeast artificial chromosomes for fluorescence in situ hybridization.
    Cytogenet Cell Genet. 1994;65(1-2):108-10 PMID: 8404060
  10. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region.
    Nat Genet. 1992 Dec;2(4):265-9 PMID: 1303277
  11. Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes.
    Am J Hum Genet. 1994 May;54(5):741-7 PMID: 8178815
  12. Maternal imprinting of human SNRPN, a gene deleted in Prader-Willi syndrome.
    Nat Genet. 1994 Feb;6(2):163-7 PMID: 7512861
  13. Allele specificity of DNA replication timing in the Angelman/Prader-Willi syndrome imprinted chromosomal region.
    Nat Genet. 1994 Jan;6(1):41-6 PMID: 8136833
  14. Functional imprinting and epigenetic modification of the human SNRPN gene.
    Hum Mol Genet. 1993 Dec;2(12):2001-5 PMID: 8111367
  15. Molecular definition of the Prader-Willi syndrome chromosome region and orientation of the SNRPN gene.
    Hum Mol Genet. 1993 Dec;2(12):1991-4 PMID: 8111365
  16. Tissue-specific expression and cDNA cloning of small nuclear ribonucleoprotein-associated polypeptide N.
    Proc Natl Acad Sci U S A. 1988 Jul;85(14):5296-300 PMID: 2969109
  17. Genomic imprinting and candidate genes in the Prader-Willi and Angelman syndromes.
    Curr Opin Genet Dev. 1993 Jun;3(3):445-56 PMID: 8353420
  18. The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis.
    N Engl J Med. 1992 Jun 11;326(24):1599-607 PMID: 1584261
  19. Uniparental disomy explains the occurrence of the Angelman or Prader-Willi syndrome in patients with an additional small inv dup(15) chromosome.
    J Med Genet. 1993 Sep;30(9):756-60 PMID: 8411071
  20. On the parental origin of de novo mutation in man.
    J Med Genet. 1991 Apr;28(4):217-23 PMID: 1677423
  21. Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.
    Nat Genet. 1995 Apr;9(4):395-400 PMID: 7795645
  22. Gene structure, DNA methylation, and imprinted expression of the human SNRPN gene.
    Am J Hum Genet. 1996 Feb;58(2):335-46 PMID: 8571960
  23. Prader-Willi syndrome: current understanding of cause and diagnosis.
    Am J Med Genet. 1990 Mar;35(3):319-32 PMID: 2309779
  24. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region.
    Nat Genet. 1992 Dec;2(4):259-64 PMID: 1303276
  25. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction.
    Am J Hum Genet. 1989 Mar;44(3):388-96 PMID: 2916582
  26. Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome.
    Nature. 1989 Nov 16;342(6247):281-5 PMID: 2812027
  27. The gene encoding the small nuclear ribonucleoprotein-associated protein N is expressed at high levels in neurons.
    J Biol Chem. 1992 Apr 25;267(12):8521-9 PMID: 1533223
  28. New insights reveal complex mechanisms involved in genomic imprinting.
    Am J Hum Genet. 1994 May;54(5):733-40 PMID: 8178814
  29. A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.
    Nat Genet. 1992 Dec;2(4):270-4 PMID: 1303278
  30. A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes.
    Genomics. 1992 Aug;13(4):917-24 PMID: 1505981
  31. Imprinting analysis of three genes in the Prader-Willi/Angelman region: SNRPN, E6-associated protein, and PAR-2 (D15S225E).
    Hum Mol Genet. 1994 Feb;3(2):309-15 PMID: 8004100
  32. Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by YAC cloning and FISH analysis.
    Hum Mol Genet. 1992 Sep;1(6):417-25 PMID: 1363801
  33. Nonreciprocal and jumping translocations of 15q1----qter in Prader-Willi syndrome.
    Am J Med Genet. 1990 Nov;37(3):311-7 PMID: 2260556
  34. A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene.
    Genomics. 1993 Dec;18(3):546-52 PMID: 8307564
  35. Modification of 15q11-q13 DNA methylation imprints in unique Angelman and Prader-Willi patients.
    Hum Mol Genet. 1993 Sep;2(9):1377-82 PMID: 8242060
  36. Translocations in Prader-Willi syndrome.
    Clin Genet. 1983 Apr;23(4):304-7 PMID: 6851221
  37. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome.
    N Engl J Med. 1981 Feb 5;304(6):325-9 PMID: 7442771
  38. Characterization of a methylation imprint in the Prader-Willi syndrome chromosome region.
    Hum Mol Genet. 1993 Dec;2(12):1995-9 PMID: 8111366
Article Info
Journal
Human molecular genetics
Abbr.
Hum Mol Genet
ISSN
0964-6906
DOI
10.1093/hmg/5.4.517
Published
1996-04-00
Pages
517-24
Language
English
Region
England
NLM ID
9208958
PMCID
PMC6057871
Subset
IM
Grants
NICHD NIH HHS · R01 HD031491 · United States
NICHD NIH HHS · HD31491 · United States
External Links
PubMed source DOI: 10.1093/hmg/5.4.517 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2