Chitty Lyn S, Kistler James, Akolekar Ranjit, Liddle Stuart, Nicolaides Kypros, Levett Lisa
University College London Institute of Child Health and Fetal Medicine Unit, UCLH NHS Foundation Trust, London, UK.
J Matern Fetal Neonatal Med. 2012 Aug;25(8):1383-6. doi: 10.3109/14767058.2011.636093. Epub 2011 Dec 6.
To determine whether molecular karyotyping using multiple ligation probe amplification (MLPA) is a reliable alternative for quick and accurate diagnosis of fetal chromosomal abnormalities.
MLPA, using specialised probe sets designed to detect aneuploidy, major chromosomal rearrangements and recognised microdeletion syndromes, was used to analyse chorionic villi or amniocytes left after traditional karyotyping of 476 fetuses for clinical indications.
An abnormal result was obtained in 190 cases, including 124 trisomies, 21 sex chromosome anomalies, 14 triploidies, and 31 rearrangements or mosaics. All trisomies were detected by all three techniques, but triploidies were only detected by karyotyping and QF-PCR. In 19 of the 31 cases of rearrangements or mosaicism there was an uncertain or high risk of adverse outcome. Traditional karyotyping detected 13 of the 19 pathogenic rearrangements, MLPA detected 18, and QF-PCR did not detect any.
MLPA, using specialized probe sets, detects more chromosomal rearrangements, conferring significant risk of adverse outcome than karyotyping. A combination of qfPCR and MLPA could be a good, rapid alternative to current practice. In the future, used in conjunction with non-invasive prenatal diagnosis based on cell free fetal DNA it might provide a rapid and efficient approach to fetal karyotyping.
确定使用多重连接探针扩增技术（MLPA）进行分子核型分析是否是快速准确诊断胎儿染色体异常的可靠替代方法。
MLPA使用专门设计用于检测非整倍体、主要染色体重排和公认的微缺失综合征的探针组，对476例因临床指征进行传统核型分析后剩余的绒毛膜绒毛或羊水细胞进行分析。
190例获得异常结果，包括124例三体、21例性染色体异常、14例三倍体以及31例重排或嵌合体。所有三体均被三种技术检测到，但三倍体仅被核型分析和QF-PCR检测到。在31例重排或嵌合体病例中，19例存在不良结局的不确定性或高风险。传统核型分析检测到19例致病性重排中的13例，MLPA检测到18例，QF-PCR未检测到任何重排。
使用专门探针组的MLPA比核型分析能检测到更多染色体重排，且不良结局风险显著。QF-PCR和MLPA联合使用可能是当前做法的一种良好、快速的替代方法。未来，与基于游离胎儿DNA的无创产前诊断结合使用，它可能为胎儿核型分析提供一种快速有效的方法。
