Prenatal diagnosis and clinical counseling for fetal chromosomal reciprocal translocations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical effect of fetal chromosomal reciprocal translocation in order to optimize procedures for prenatal diagnosis and clinical counseling.</p><p><b>METHODS</b>Conventional G-banding karyotype analysis was performed on 7901 amniotic fluid samples. For fetuses found to have carried a reciprocal translocation, karyotypes of their parents were checked. Fetuses with de novo translocations also underwent microarray analysis to exclude small deletions, and were subjected to prenatal ultrasound monitoring till birth and one year follow-up. Those with de novo translocations were followed till 3 years old.</p><p><b>RESULTS</b>A total of 24 fetal reciprocal translocations have been identified, which gave a detection rate of 0.30%. Analysis of parental karyotypes has found reciprocal translocations in 17 cases, including 9 maternal and 8 paternal cases. The remaining 4 were of de novo mutations, for which parental examination was refused in three cases. For fetuses with inherited translocations, prenatal ultrasound monitoring and follow-up results were all normal. For those with de novo translocations, although gene chip analysis has failed to detect copy number variations (CNVs), prenatal ultrasound and follow-up results had found three with abnormal outcome. These included 1 case with reciprocal translocation involving the X chromosome and an autosome.</p><p><b>CONCLUSION</b>For prenatally detected reciprocal chromosome translocations, parental origin should be traced. Gene chip analysis can help to exclude small deletions and duplications. However, ultrasound monitoring and follow-up after birth are equally important. Based on comprehensive analysis of the results of combined testing, accurate counseling can be provided.</p>

SNP-chip technology for identification of origins for prenatally detected marker chromosomes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the origin of 1 prenatally detected small supernumerary marker chromosome (sSMC) using SNP-chip technology, and to deduce the underlying mechanism.</p><p><b>METHODS</b>The fetal sample was subjected to karyotype analysis. The identified sSMC was subjected to genom wide scan using a SNP microarray chip. The results were validated with fluorescence in situ hybridization (FISH).</p><p><b>RESULTS</b>The karyotype of the fetus was determined as 46, X, +mar, which was verified by SNP microarray chip analysis as Yp11.2-11.3 duplication, along with loss of Yq11.2 region, FISH analysis has confirmed that the sSMC has derived from the Y chromosome.</p><p><b>CONCLUSION</b>The karyotype of the fetus was determined as 46, X, idic(Y) (pter→ p11.2::11.2→ pter). Regional deletion of Yq11.2 has been associated with male azoospermia. SNP chip analysis can exclude minor deletions and duplications with a size of more than 1 Mb, which may be applied for verifying difficult cases as well as microdeletion and duplication syndromes upon prenatal diagnosis.</p>

Rapid and high-throughput multiplex ligation-dependent probe amplification for diagnosis of chromosome aneuploidy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the diagnostic value of multiplex ligation-dependent probe amplification (MLPA) for detection of common chromosome aneuploidy in amniotic fluid (AF) cells in order to obtain an accurate, rapid, cost-effective and high-throughput method in routine prenatal clinical practice.</p><p><b>METHODS</b>The MLPA test was performed on 500 AF samples by using kit P095 and the results were obtained by using analysis software RH-MLPA-v511. The results were compared with that from fluorescence in situ hybridization (FISH) and traditional karyotyping (TK). The technical critical issues were analyzed in routine diagnostic application.</p><p><b>RESULTS</b>The absolute specificity and sensitivity of the MLPA test to detect the aneuploidy were 100%. For the 500 AF samples, the success rate of the MLPA tests was 97%. Among them 92% were finished within three working days and 5% required more days for repeating. The test failure rate was 3%. The results confirmed that for the 38 detectable aneuploid samples, the probe reliability weighted mean ratio values were more than 4SD compared to normal diploids and the 2 suspected trisomy samples were more than 2SD. In this study, authors analyzed hybridization efficiencies of 8 probes for chromosome 21, and the presence of a trisomy was considered if at least 4 of the 8 probes gave probe ratio of >1.3.</p><p><b>CONCLUSION</b>Thedata suggested that MLPA is a rapid, simple and reliable method for large scale testing for aneuploidy of chromosomes 13, 18, 21, X, or Y in AF. The MLPA technology is complementary to AF culture and valuable for prenatal diagnosis.</p>