摘要目的 探讨Angelman综合征(Angelman syndrome,AS)及Prader-Willi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(single nucleotide polymorphism microarrays,SNP array)在其诊断中所起的作用.方法 应用SNP array、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4.8～7.0 Mb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) (q11q11),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;SNP array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.

abstractsObjective 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 Mb 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 be 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.