单核苷酸多态微阵列技术确诊Wolf-Hirschhorn综合征一例

A case of Woif-Hirschhorn syndrome diagnosed by single nucleotide polymorphism array

目的探讨1例多发畸形伴癫痫患儿的遗传学病因，分析该患儿基因组拷贝数变异（copynumbervariations，CNVs）与临床表型的关系。方法对患儿及其父母行外周血淋巴细胞G显带染色体核型分析，对患儿应用单核苷酸多态性微阵列芯片技术（singlenucleotidepolymorphismsarray，SNP—array）检测其染色体结构改变，之后用荧光原位杂交技术（fluorescenceinsituhybridization，FISH）进行验证。结果患儿染色体核型为46，XX，del（4）（p15），其父母外周血核型分析未见异常。SNP—array分析结果显示患儿4p16．3p15．33区域存在13．3Mb的杂合性缺失，该缺失与Wolf-Hirschhorn综合征相关。FISH结果证实了此缺失的存在，结合父母的核型与临床表型确认为新发缺失。结论根据患儿的临床表型及染色体缺失的片段明确诊断Wolf-Hirschhorn综合征一例。SNP—array技术可以进一步明确缺失的具体区域及所包含的基因，与传统的细胞遗传学分析方法相比，具有高分辨、高准确度的优点，可为遗传学检测提供更为详细的信息。

Objective To explore the genetic causes for a child with multiple congenital malformations and epilepsy through analysis of copy number variations, and to correlate the genotype with the phenotype. Methods G-banding karyotyping was performed on the child and her parents. Single nucleotide polymorphisms array （SNP-array） was used to map the exact chromosomal breakpoints in the proband. The result was validated with fluorescence in situ hybridization （FISH）. Results G banding analysis suggested that the proband had a karyotype of 46 ,XX,del（4）（p15）, while both of his parents had a normal karyotype. SNP array has identified a hemizygous deletion of 13. 3 Mb on chromosome 4p16.3p15.33, which has been implicated in WolLHirschhorn syndrome. FISH assay has confirmed the de novo origin of the deletion, with the karyotype and clinical phenotype of both parents taken into consideration. Conclusion A case of Wolf-Hirschhorn syndrome has been diagnosed by clinical manifestation and karyotyping analysis. Compared with conventional karyotyping analysis, SNP-array has greater resolution and accuracy, and can provide useful information for genetic counseling.