Kirchhoff Maria, Bisgaard Anne-Marie, Bryndorf Thue, Gerdes Tommy
Chromosome Laboratory, Department of Clinical Genetics, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen ø, Denmark.
Eur J Med Genet. 2007 Jan-Feb;50(1):33-42. doi: 10.1016/j.ejmg.2006.10.002. Epub 2006 Oct 10.
MLPA analysis for a panel of syndromes with mental retardation (MRS-MLPA) was used for investigation of 258 mentally retarded and dysmorphic patients with normal conventional karyotypes (P064 probe set, MRC-Holland, for detection of (micro)deletions associated with 1p36-deletion, Sotos, Williams-Beuren, Prader-Willi, Angelman, Miller-Dieker, Smith-Magenis, and 22q11-deletion syndromes). Patients were initially referred for HR-CGH analysis and MRS-MLPA was performed retrospectively. MRS-MLPA analysis revealed imbalances in 15/258 patients (5.8%). Ten deletions were identified, including deletions of 1p36, 5q35 (Sotos syndrome), 7q11 (Williams-Beuren syndrome), 17p11 (Smith-Magenis syndrome), 15q11 (Angelman syndrome) and 22q11. Duplications were detected in 5q35, 7q11, 17p13, 17p11 and 22q11. We reviewed another 170 patients referred specifically for MRS-MLPA analysis. Eighty of these patients were referred with a clinical suspicion of a specific syndrome, which was confirmed in 17 patients (21.3%). The remaining 90 patients were referred because of mental retardation and dysmorphism but without suspicion of a specific syndrome. Seven imbalances, including four duplications, were detected in these 90 patients (7.8%). Clinical data regarding three patients investigated by MRS-MLPA are presented. The imbalances carried by these patients include a small interstitial 1p36 deletion, a small duplication of 5q35 (encompassing the NSD1 gene, which is deleted/mutated in Sotos syndrome) and a duplication of 7q11 (reciprocal of the Williams-Beuren syndrome deletion), respectively. MRS-MLPA allows testing for a number of micro-deletions/-duplications in a single experiment, thereby filling a gap between array techniques and single locus techniques. MRS-MLPA combined with Subtelomeric MLPA represents an attractive first test in a clinical algorithm for mental retardation.
采用智力发育迟缓相关综合征多重连接探针扩增分析（MRS-MLPA）对258例常规核型正常的智力发育迟缓及畸形患者进行检测（使用MRC-Holland公司的P064探针组，检测与1p36缺失、索托斯综合征、威廉姆斯-博伦综合征、普拉德-威利综合征、安吉尔曼综合征、米勒-迪克尔综合征、史密斯-马吉尼斯综合征及22q11缺失综合征相关的（微）缺失）。患者最初因高分辨比较基因组杂交（HR-CGH）分析前来就诊，MRS-MLPA检测为回顾性进行。MRS-MLPA分析显示，258例患者中有15例（5.8%）存在失衡。共检测到10例缺失，包括1p36、5q35（索托斯综合征）、7q11（威廉姆斯-博伦综合征）、17p11（史密斯-马吉尼斯综合征）、15q11（安吉尔曼综合征）及22q11缺失。还在5q35、7q11、17p13、17p11及22q11检测到重复。我们回顾了另外170例专门因MRS-MLPA分析前来就诊的患者。其中80例患者临床怀疑患有特定综合征，17例（21.3%）得到确诊。其余90例患者因智力发育迟缓和畸形前来就诊，但无特定综合征的怀疑。这90例患者中检测到7例失衡，包括4例重复（7.8%）。文中展示了3例接受MRS-MLPA检测患者的临床资料。这些患者所携带的失衡分别包括一个小的间质性1p36缺失、一个5q35小重复（包含索托斯综合征中缺失/突变的NSD1基因）及一个7q11重复（威廉姆斯-博伦综合征缺失的对应区域）。MRS-MLPA可在一次实验中检测多种微缺失/微重复，从而填补了阵列技术和单基因座技术之间的空白。MRS-MLPA与亚端粒MLPA相结合，是智力发育迟缓临床诊断流程中一项有吸引力的初步检测方法。
