Ahlbom B E, Goetz P, Korenberg J R, Pettersson U, Seemanova E, Wadelius C, Zech L, Annerén G
Department of Clinical Genetics, Uppsala University, Children's Hospital, Sweden.
Am J Med Genet. 1996 Jun 28;63(4):566-72. doi: 10.1002/(SICI)1096-8628(19960628)63:4<566::AID-AJMG10>3.0.CO;2-G.
Down syndrome (DS) is caused in most cases by the presence of an extra chromosome 21. It has been shown that the DS phenotype is produced by duplication of only a small part of the long arm of chromosome 21, the 21q22 region, including and distal to locus D21S55. We present molecular investigations on a woman with clinically typical DS but apparently normal chromosomes. Her parents were consanguineous and she had a sister with a DS phenotype, who died at the age of 15 days. Repeated cytogenetic investigations (G-banding and high resolution banding) on the patient and her parents showed apparently normal chromosomes. Autoradiographs of quantitative Southern blots of DNAs from the patient, her parents, trisomy 21 patients, and normal controls were analyzed after hybridization with unique DNA sequences regionally mapped on chromosome 21. Sequences D21S59, D21S1, D21S11, D21S8, D21S17, D21S55, ERG, D21S15, D21S112, and COL6A1 were all found in two copies. Fluorescent in situ hybridization with a chromosome 21-specific genomic library showed no abnormalities and only two copies of chromosome 21 were detected. Nineteen markers from the critical region studied with polymerase chain reaction amplification of di- and tetranucleotide repeats did not indicate any partial trisomy 21. From this study we conclude that the patient does not have any partial submicroscopic trisomy for any segment of chromosome 21. It seems reasonable to assume that she suffers from an autosomal recessive disorder which is phenotypically indistinguishable from DS.
唐氏综合征（DS）多数情况下是由额外的一条21号染色体所致。研究表明，DS表型是由21号染色体长臂一小部分（21q22区域）的重复产生的，该区域包括基因座D21S55及其远端。我们对一名临床症状典型但染色体看似正常的女性进行了分子研究。她的父母是近亲，她有一个患有DS表型的妹妹，妹妹在15天时夭折。对该患者及其父母进行的反复细胞遗传学检查（G显带和高分辨显带）显示染色体看似正常。用区域定位在21号染色体上的独特DNA序列与患者、其父母、21三体患者及正常对照的DNA进行定量Southern杂交，对放射自显影片进行分析。序列D21S59、D21S1、D21S11、D21S8、D21S17、D21S55、ERG、D21S15、D21S112和COL6A1均发现有两个拷贝。用21号染色体特异性基因组文库进行荧光原位杂交未发现异常，仅检测到两个拷贝的21号染色体。用聚合酶链反应扩增二核苷酸和四核苷酸重复序列对关键区域的19个标记进行研究，未显示任何2号染色体部分三体。从这项研究我们得出结论，该患者21号染色体的任何片段不存在任何部分亚显微三体。推测她患有一种常染色体隐性疾病，其表型与DS难以区分，这似乎是合理的。
