PMID- 8641697
OWN - NLM
STAT- MEDLINE
DCOM- 19960712
LR  - 20190722
IS  - 0340-6717 (Print)
IS  - 0340-6717 (Linking)
VI  - 97
IP  - 6
DP  - 1996 Jun
TI  - Routine screening for microdeletions by FISH in 77 patients suspected of having 
      Prader-Willi or Angelman syndromes using YAC clone 273A2 (D15S10).
PG  - 784-93
AB  - About 70% of patients with Prader-Willi syndrome (PWS) and Angelman syndrome (AS) 
      have a common interstitial de novo microdeletion encompassing paternal (PWS) or 
      maternal (AS) loci D15S9 to D15S12. Most of the non-deletion PWS patients and a 
      small number of non-deletion AS patients have a maternal or paternal uniparental 
      disomy (UPD) 15, respectively. Other chromosome 15 rearrangements and a few 
      smaller atypical deletions, some of the latter being associated with an abnormal 
      methylation pattern, are rarely found. Molecular and fluorescence in situ 
      hybridization (FISH) analysis have both been used to diagnose PWS and AS. Here, 
      we have evaluated, in a typical routine cytogenetic laboratory setting, the 
      efficiency of a diagnostic strategy that starts with a FISH deletion assay using 
      Alu-PCR (polymerase chain reaction)-amplified D15S10-positive yeast artificial 
      chromosome (YAC) 273A2. We performed FISH in 77 patients suspected of having PWS 
      (n = 66) or AS (n = 11) and compared the results with those from classical 
      cytogenetics and wherever possible with those from DNA analysis. A FISH deletion 
      was found in 16/66 patients from the PWS group and in 3/11 patients from the AS 
      group. One example of a centromere 15 co-hybridization performed in order to 
      exclude cryptic translocations or inversions is given. Of the PWS patients, 14 
      fulfilled Holm's criteria, but two did not. DNA analysis confirmed the common 
      deletion in all patients screened by the D15S63 methylation test and in 
      restriction fragment length polymorphism dosage blots. In 3/58 non-deletion 
      patients, other chromosomal aberrations were found. Of the non-deleted group, 27 
      subjects (24 PWS, 3 AS) were tested molecularly, and three patients with an 
      uniparental methylation pattern were found in the PWS group. The other 24/27 
      subjects had neither a FISH deletion nor uniparental methylation, but two had 
      other cytogenetic aberrations. Given that cytogenetic analysis is indispensable 
      in most patients, we find that the FISH deletion assay with YAC 273A2 is an 
      efficient first step for stepwise diagnostic testing and mutation-type analysis 
      of patients suspected of having PWS or AS.
FAU - Erdel, M
AU  - Erdel M
AD  - Institut fur Medizinische Biologie und Humangenetik, Leopold-Franzens-Universitat 
      Innsbruck, Austria.
FAU - Schuffenhauer, S
AU  - Schuffenhauer S
FAU - Buchholz, B
AU  - Buchholz B
FAU - Barth-Witte, U
AU  - Barth-Witte U
FAU - Kochl, S
AU  - Kochl S
FAU - Utermann, B
AU  - Utermann B
FAU - Duba, H C
AU  - Duba HC
FAU - Utermann, G
AU  - Utermann G
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Hum Genet
JT  - Human genetics
JID - 7613873
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Angelman Syndrome/diagnosis/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Banding
MH  - *Chromosome Deletion
MH  - Chromosomes, Artificial, Yeast
MH  - Chromosomes, Human, Pair 15/*genetics
MH  - DNA/chemistry
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Infant
MH  - Male
MH  - Methylation
MH  - Phenotype
MH  - Prader-Willi Syndrome/diagnosis/*genetics
MH  - Sensitivity and Specificity
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1007/BF02346190 [doi]
PST - ppublish
SO  - Hum Genet. 1996 Jun;97(6):784-93. doi: 10.1007/BF02346190.