Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic 
mutations causes Sotos syndrome (SoS). In 46 of the 49 Japanese deletion cases, 
common deletion breakpoints were located at two flanking low copy repeats 
(LCRs), implying that non-allelic homologous recombination (NAHR) between LCRs 
is the major mechanism for the common deletion. In the other three cases of 
atypical deletions, the mechanism(s) of deletions remains unanswered. We 
characterized the atypical microdeletions using fluorescence in situ 
hybridization (FISH), quantitative real-time polymerase chain reaction (qPCR), 
and Southern blot hybridization. All the deletion breakpoints in the three cases 
were successfully determined at the nucleotide level. Two deletions are 1.07 Mb 
(SoS19) and 1.23 Mb (SoS109) in size, and another consisted of two deletions 
with sizes of 28 kb and 0.72 Mb, intervened by an intact 29-kb segment (SoS44). 
All deletions were smaller than a typical 1.9-Mb common deletion. Alu elements 
were identified in both deletion breakpoints in SoS19, one of deletion 
breakpoints in SoS109, and both deletion breakpoints of the proximal 28-kb 
deletion in SoS44. Alu-mediated NAHR is strongly suggested at least in two of 
atypical deletions. Finally, qPCR is a very useful method to determine deletion 
breakpoints even in repeat-related regions.