一例类似Prader-Willi综合征表型患者的染色体1p36．3隐匿缺失检测

Identification of a cryptic lp36. 3 microdeletion in a patient with Prader-Wiili-like syndrome features

目的 对1例具有类似Prader-Willi综合征（Prader-Will-like syndrome,PWS）表型患者进行核型分析,确诊其病因.方法 应用高分辨染色体显带技术分析核型及甲基化PCR技术分析15号染色体的遗传印迹区,应用多重连接依赖性探针扩增（multiplex ligation-dependent probe amplification,MLPA）技术筛查患者染色体亚端粒区的异常,经荧光原位杂交（fluorescence in situ hybridization,FISH）验证并结合实时定量PCR进一步确定患者染色体的缺失区域.结果 高分辨染色体检测未发现患者核型异常,甲基化PCR未发现患者的15号染色体遗传印迹基因异常,MLPA分析显示患者存在1p亚端粒区缺失,该结果得到1p亚端粒区探针的FISH证实.进一步选择1p36区域的3个BAC探针进行FISH分析,结合实时定量PCR技术,显示缺失区域位于1p36.3区的4.2 Mb范围内,家系分析显示患者为新发生的染色体异常.确诊为1p36缺失综合征.结论 对类似PWS表型的患者,应进一步做细胞分子学诊断,以明确其发病原因.

Objective To determine the karyotype of a patient with Prader-Willi-like syndrome features. Methods Chromosomal high resolution banding was carried out to analyze the karyotype of the patient, and methylation-specific PCR was used to analyze the imprinting region of chromosome 15.Subtelomeric region was screened by multiplex ligation-dependent probe amplification （MLPA）, and fluorescent in situ hybridization （FISH） and real-time quantitative PCR were further performed to identify the deleted region. Results No abnormality was discovered by high resolution karyotype analysis and methylation-specific PCR studies. MLPA analysis showed that the patient had a deletion of 1p subtelomeric area, which was confirmed by FISH analysis. The deleted region was shown within a 4.2 Mb in the distal 1p by 3 BAC FISH probes of 1p36 combined with real-time PCR technique. Family pedigree investigation showed the chromosome abnormality was de novo. Therefore, partial monosomy 1p36 was likely responsible for the mental retardation of the patient. Conclusion Molecular cytogenetic techniques should be performed to those patients with Prader-Willi-like syndrome features, to determine their karyotypes.