We have previously described a series of patients in whom the deletion of 1-2 
megabases (Mb) of DNA from the tip of the short arm of chromosome 16 (band 
16p13.3) is associated with alpha-thalassemia/mental retardation syndrome 
(ATR-16). We now show that one of these patients has a de novo truncation of the 
terminal 2 Mb of chromosome 16p and that telomeric sequence (TTAGGG)n has been 
added at the site of breakage. This suggests that the chromosomal break, which 
is paternal in origin and which probably arose at meiosis, has been stabilized 
in vivo by the direct addition of the telomeric sequence. Sequence comparisons 
of this breakpoint with that of a previously described chromosomal truncation 
(alpha alpha)TI do not reveal extensive sequence homology. However, both 
breakpoints show minimal complementarity (3-4 bp) to the proposed RNA template 
of human telomerase at the site at which telomere repeats have been added. 
Unlike previously characterized individuals with ATR-16, the clinical features 
of this patient appear to be solely due to monosomy for the terminal portion of 
16p13.3. The identification of further patients with "pure" monosomy for the tip 
of chromosome 16p will be important for defining the loci contributing to the 
phenotype of this syndrome.