Fluorescence in situ hybridization (FISH) using two cosmid probes (41A and P13) 
from the Miller-Dieker syndrome (MDS) critical region in 17p13.3 was performed 
in a blinded comparison of three MDS patients with submicroscopic deletions and 
in four normal relatives used as controls. The controls showed both chromosome 
17 homologues labeled in 85%-95% of cells, while each patient showed only one 
homologue labeled in 75%-80% of cells. Two MDS patients with cryptic 
translocations were also studied. In one case, a patient and her mother had the 
same der(17) (p+), but the reciprocal product of the translocation could not be 
identified in the mother by G-banding (i.e., it was a "half-cryptic" 
translocation). FISH revealed a 3q;17p translocation. The other case involved a 
patient with apparently normal karyotype. Because a large molecular deletion was 
found, a translocation involving two G-negative telomeres (i.e., a 
"full-cryptic" translocation) was postulated. FISH studies on her father and 
normal brother showed an 8q;17p translocation. These studies demonstrate that in 
situ hybridization is an efficient method for deletion detection in 
Miller-Dieker syndrome. More important, parental studies by FISH on patients 
demonstrating molecular deletions and a normal karyotype may identify cryptic 
translocation events, which cannot be detected by other molecular genetic 
strategies. Similar in situ strategies for deletion detection can be developed 
for other microdeletion syndromes, such as Prader-Willi/Angelman syndrome or 
DiGeorge syndrome.