12例Angelman综合征及Prader-Willi综合征患者的临床表型和遗传学分析  

Phenotype-genotype correlation analysis of 12 cases with Angelman/Prader-Willi syndrome

作　　者：陈晨[1,2,3] 彭莹[1] 夏艳[1] 李浩贤[1] 朱慧敏[1] 潘乾[1] 尹飞[2,3] 邬玲仟 

机构地区：[1]中南大学医学遗传学国家重点实验室,长沙410078 [2]湘雅医院儿科 [3]湖南省儿童智力障碍研究中心

出　　处：《中华医学遗传学杂志》2014年第6期708-712,共5页Chinese Journal of Medical Genetics

基　　金：国家重点基础研究发展计划（973计划）资助项目（2012CB944601）;湖南省博士后科研资助专项计划（2014RS4007）

摘　　要：目的探讨Angelman综合征（Angelman syndrome，AS）及Prader_wmi综合征（Prader-Willi syndrome，PWS）患者的临床表型与基因型关系及单核苷酸多态性微阵列技术（singlenucleotide polymorphism microarrays，SNParray）在其诊断中所起的作用。方法应用SNParray、荧光原位杂交及染色体核型分析对12例AS及PWS患者进行精确的遗传学诊断及分型，并结合临床特点进行相关分析。结果12例患者中，11例存在染色体15q11．2-13区域4．8-7．0Mb缺失，1例为该区域单亲二体（uniparental disomy，UPD）；根据近端断裂点位置，7例患者为缺失I型，4例为缺失Ⅱ型，两组临床表现无明显差异；UPD患者语言运动发育相对较好；荧光原位杂交证实6例缺失患者为新发突变，其同胞再患病概率〈1％。9例患者行染色体核型分析，1例为46，XY，？del（15）（qllqil），余8例无异常。结论缺失I型及缺失Ⅱ型As及PWS患者的临床表型差异有待进一步研究；SNParray可对缺失型及UPD型As／PWS患者进行确诊和分型，有助于表型-基因型关联研究及AS及PWS发病机制研究。Objective To investigate the genotype-phenotype correlation in patients with Angelman syndrome/Prader-Willi syndrome （AS/PWS） and assess the application value of high-resolution single nucleotide polymorphism microarrays （SNP array） for such diseases. Methods Twelve AS/PWS patients were diagnosed through SNP array, fluorescence in situ hybridization （FISH） and karyotype analysis. Clinical characteristics were analyzed. Results Deletions ranging from 4.8 Mh to 7.0 Mb on chromosome 15q11.2-13 were detected in 11 patients. Uniparental disomy （UPD） was detected in only 1 patient. Patients with deletions could be divided into 2 groups, including 7 cases with class I and 4 with class Ⅱ. The two groups however had no significant phenotypic difference. The UPD patient had relatively better development and language ability. Deletions of 6 patients were confirmed by FISH to be of de novo in origin. The risk to their sibs was determined to be 〈1%. Conclusion The phenotypic differences between AS/ PWS patients with class I and class Ⅱ deletion need to he further studied. SNP array is useful in detecting and distinguishing of patients with deletion or UPD. This method may be applied for studying the genotype- phenotype association and the mechanism underlying AS/PWS.

关 键 词：ANGELMAN综合征 PRADER-WILLI综合征 SNP array 遗传学诊断 表型分析 

分 类 号：R394[医药卫生—医学遗传学]