PMID- 17867985
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20221207
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 45
IP  - 8
DP  - 2007
TI  - Highest accuracy of combined consensus clinical criteria and SNRPN gene molecular 
      markers in diagnosis of Prader-Willi syndrome in Thai patients.
PG  - 972-80
AB  - BACKGROUND: Prader-Willi Syndrome (PWS) is a complex human genetic disease 
      arising from a loss of paternal allele expression of imprinting genes on 
      chromosome 15q11-q13. Normally the CpG islands at this site are heavily 
      methylated in the maternal allele, but unmethylated in the paternal allele and 
      therefore activated in gene expression. only the methylated allele should present 
      in pws patients when methylation-specific pcr (msp) is analyzed. METHODS: This 
      paper reports an analysis of PWS in Thai patients using consensus diagnostic 
      criteria based on a combination of clinical data, basic G-banding and 
      fluorescence in situ hybridization (FISH) cytogenetics, PCR-based methylation 
      assay, and bisulfite sequencing of the CpG islands of SNRPN to confirm 15q 
      deletion or the methylation pattern of the SNRPN promoter and exon 1. Lack of 
      complete clinical reports or inadequacy of the minimum laboratory support 
      required had made it difficult to diagnose PWS, Angelman syndrome and other 
      microdeletion disorders. RESULTS: Accuracy of 100% was obtained for diagnosis of 
      the PWS study patients using the minimum requirements necessary. A total of 20 
      patients were diagnosed as PWS based on clinical criteria and the scoring tool 
      for PWS, and the same approach was applied to four separate patients with some 
      unmatched criteria but phenotypic similarity to PWS. Findings showed that 70% of 
      those clinically diagnosed as PWS patients (14/20) had a deletion at 15q11-q13 
      according to FISH, while all 20 patients showed MSP positive of SNRPN gene. Six 
      cases (30%) without a paternal deletion were confirmed to have maternal 
      uniparental disomy (mUPD) of PWS by MSP and methylation sequencing approaches. 
      Noteworthy, two of the six cases with mUPD were 3.5 year-old twins. None of the 
      five cases with scores lower than the reported consensus criteria showed positive 
      G-band, FISH or MSP results. CONCLUSIONS: We demonstrate here the high power of 
      combining clinical findings, FISH and MSP in definitive diagnosis of PWS and in 
      distinguishing between the two major different types of molecular mechanisms. No 
      false positives or false negatives were observed in our analysis.
FAU - Promkan, Moltira
AU  - Promkan M
AD  - Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol 
      University, Bangkok, Thailand.
FAU - Teingtat, Somporn
AU  - Teingtat S
FAU - Stheinkijkarnchai, Atchara
AU  - Stheinkijkarnchai A
FAU - Wasant, Pornswan
AU  - Wasant P
FAU - Patmasiriwat, Pimpicha
AU  - Patmasiriwat P
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Autoantigens)
RN  - 0 (Genetic Markers)
RN  - 0 (Ribonucleoproteins, Small Nuclear)
RN  - 0 (SNRPN protein, human)
RN  - 0 (snRNP Core Proteins)
SB  - IM
MH  - Asian People/genetics
MH  - Autoantigens/*genetics
MH  - Child
MH  - Child, Preschool
MH  - CpG Islands
MH  - DNA Methylation
MH  - Diagnostic Techniques and Procedures/*standards
MH  - Female
MH  - Genetic Markers
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Prader-Willi Syndrome/*diagnosis/genetics
MH  - Ribonucleoproteins, Small Nuclear/*genetics
MH  - Sensitivity and Specificity
MH  - Sequence Analysis, DNA
MH  - Sequence Deletion
MH  - Thailand/epidemiology
MH  - Uniparental Disomy
MH  - snRNP Core Proteins
EDAT- 2007/09/18 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/09/18 09:00
PHST- 2007/09/18 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/09/18 09:00 [entrez]
AID - 10.1515/CCLM.2007.271 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 2007;45(8):972-80. doi: 10.1515/CCLM.2007.271.