Lamb J, Harris P C, Wilkie A O, Wood W G, Dauwerse J G, Higgs D R
Medical Research Council Molecular Haematology Unit, John Radcliffe Hospital, Oxford, England.
Am J Hum Genet. 1993 Apr;52(4):668-76.
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.
我们之前描述过一系列患者，他们的16号染色体短臂末端（16p13.3带）缺失1 - 2兆碱基（Mb）的DNA与α地中海贫血/智力发育迟缓综合征（ATR - 16）相关。我们现在发现其中一名患者的16号染色体短臂末端2 Mb发生了新生截断，并且在断裂位点添加了端粒序列（TTAGGG）n。这表明该染色体断裂起源于父方，可能在减数分裂时发生，并且通过直接添加端粒序列在体内得以稳定。将这个断点与之前描述的染色体截断（αα）TI的断点进行序列比较，未发现广泛的序列同源性。然而，在添加端粒重复序列的位点，两个断点与人类端粒酶的推测RNA模板都显示出最小互补性（3 - 4个碱基对）。与之前已鉴定的ATR - 16个体不同，该患者的临床特征似乎完全是由于16p13.3末端部分的单体性所致。鉴定更多具有16号染色体短臂末端“纯”单体性的患者对于确定导致该综合征表型的基因座将具有重要意义。
