一4q部分三体10q部分单体患儿的分子细胞遗传分析

Cytogenetic and molecular characterization of partial trisomy 4q and partial monosomy lOq in a patient

目的确定一生长迟缓、智力低下患儿的核型，分析其染色体变异与表型的相关性，同时探讨微阵列比较基因组杂交（array-based comparative genomic hybridization，array—CGH）在临床分子细胞遗传诊断中的应用及其优越性。方法应用G显带染色体分析、array—CGH、荧光原位杂交（fluorescence in situ hybridization，FISH）和实时定量PCR（real—time quantitative PCR，RQ-PCR）对患儿及其亲属进行核型分析。结果G显带染色体分析显示患儿存在1条来源于父亲的10号衍生染色体der（10）t（4；10）（q25；q26），其父亲和祖母均是t（4；10）（q25；q26）平衡易位携带者。Array-CGH显示患儿存在4q26-q35．2三体，并将断裂点定位于4q26，此外，还发现患儿10号染色体存在一约0．54Mb的微缺失del（10）（q26．3）。FISH和RQ-PCR证实父亲和祖母也存在del（10）（q26．3）。结论del（10）（q26．3）并不导致表型异常，患儿的异常表型可归凶于4q26-q35．2三体。与传统的细胞遗传分析方法相比，arrayCGH具有高分辨率和高准确性等优点。

Objective To ascertain the karyotype of a girl with moderate mental retardation and growth retardation, perform correlation analysis between chromosomal variation and phenotype, and investigate the application and superiority of array-based comparative genomic hybridization （array-CGH） in clinical cytogenetic diagnosis. Methods G-banded chromosome analysis, array CGH, fluorescence in situ hybridization （FISH） and real-time quantitative PCR （RQPCR） were used to ascertain the karyotype of the patient and her relatives. Results G-banding analysis of the patient showed a derivative chromosome 10 with an extra fragment on its long arm terminal, both her father and grandmother had an apparently balanced translocation t（4;10）（q25;q26）. Array CGH revealed that the breakpoint on chromosome 4 was located at 4q26. In addition, a microdeletion of about 0. 54 Mb del（10）（q6. 3） was identified from the patient. FISH and RQ-PCR confirmed that the del（10） （q26. 3） was also present in both her father and grandmother. Conclusion No recognizable phenotype was associated with del（10）（q26.3）. The abnormal phenotypes presented in the patient may be ascribed to the 4q26 q35.2 triplication. Further more, compared with conventional cytogenetic analysis, array-CGH is of high resolution and high accuracy.