A diagnostic approach to identifying submicroscopic 7p21 deletions in Saethre-Chotzen syndrome: fluorescence in situ hybridization and dosage-sensitive Southern blot analysis.
OBJECTIVE
To report on the use of fluorescence in situ hybridization (FISH) and dosage-sensitive Southern blot analysis in the molecular diagnosis of patients with Saethre-Chotzen syndrome.


METHODS
FISH and dosage-sensitive Southern blot analysis utilizing TWIST gene probes were performed on patients with Saethre-Chotzen syndrome but without an identifiable TWIST sequence variation.


RESULTS
Four unrelated patients with a deletion of the TWIST gene were identified by Southern blot; one of them had a complex chromosomal rearrangement involving 7p21 and no apparent deletion by FISH, suggesting a smaller deletion in the region including the TWIST gene. A fifth patient had an abnormal TWIST gene fragment on Southern blot analysis that segregated with the disease in the family; FISH was normal in this patient, suggesting a partial deletion or rearrangement in or near the gene.


CONCLUSIONS
FISH and dosage-sensitive Southern blot analysis are useful diagnostic tools in Saethre-Chotzen syndrome without TWIST sequence variation.
Gripp
K W
KW
Division of Human Genetics and Molecular Biology, Abramson BLDG 1002, The Children's Hospital of Philadelphia, 34th & Civic Center Blvd., Philadelphia, PA 19104, USA.
Kasparcova
V
V
McDonald-McGinn
D M
DM
Bhatt
S
S
Bartlett
S P
SP
Storm
A L
AL
Drumheller
T C
TC
Emanuel
B S
BS
Zackai
E H
EH
Stolle
C A
CA
D000168:Acrocephalosyndactylia / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002875:Chromosomes / Q000648:ultrastructure; D002897:Chromosomes, Human, Pair 7; D004305:Dose-Response Relationship, Drug; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017403:In Situ Hybridization; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009687:Nuclear Proteins; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1
D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1