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OBJECTIVE@#To discuss the advantages and technical limitations of various molecular genetic techniques in the diagnosis of two infants featuring all-round developmental retardation.@*METHODS@#The two patients were initially screened by using chromosomal microarray analysis (CMA). For patient 1, his parents were also subjected to CMA analysis, and the data was analyzed by using ChAS and UPD-tool software. For patient 2, methylation-specific PCR (MS-PCR) was carried out.@*RESULTS@#Patient 1 was diagnosed with maternal uniparental disomy (UPD) type Prader-Willi syndrome (PWS) by CMA and UPD-tool family analysis. His chromosomes 15 were of maternal UPD with homology/heterology. Patient 2 was diagnosed with deletion type PWS by combined CMA and MS-PCR.@*CONCLUSION@#Correct selection of laboratory methods based on the advantages and limitations of various molecular techniques can help with diagnosis of genomic imprinting disorders and enable better treatment and prognosis through early intervention.
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OBJECTIVE@#To diagnose a 46,XN,del(11)(q14q22) fetus by non-invasive prenatal testing (NIPT), karyotype analysis and whole genome sequencing (WGS).@*METHODS@#Peripheral blood sample of the gravida was taken for NIPT screening. Blood samples of the gravida, her husband, and umbilical cord blood were also taken for chromosome karyotyping and whole genome sequencing (WGS).@*RESULTS@#NIPT screening indicated the fetus has carried partial deletion of chromosome 11, while no chromosomal abnormality was found with the cord blood sample due to the low resolution of G-banding analysis. WGS analysis of the cord blood indicated 46,XN,del(11q14.3q22.1). seq[GRCh37/hg19] (90 623 404-97 469 319)×1, 6.85 Mb. The karyotype of the fetus was eventually determined as 46,XN,del(11)(q14q22). Karyotyping analysis suggested that the gravida and her husband were 46,XX,del(11)(q14q22)[8]/46,XX[92] and 46,XY, respectively. However, neither of them was found to harbor the del(11)(q14q22) by WGS.@*CONCLUSION@#The abnormal karyotype of the fetus has derived from its mother's low percentage mosaicism. Combined NIPT, karyotyping analysis and WGS can detect chromosomal disorders with accuracy.
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<p><b>OBJECTIVE</b>To analyze a fetus with abnormal cardiac ultrasound by using various techniques and explore its genotype-phenotype correlation.</p><p><b>METHODS</b>Lymphocytes derived from umbilical cord blood sample were subjected to G-banding analysis. Short tandem repeats quantitative fluorescence PCR (STR-QF-PCR) was used for analysis of fetal DNA as an auxiliary test. Low-coverage whole genome sequencing (WGS) was used to detect chromosomal deletion/duplication which exceeded 100 kb in size.</p><p><b>RESULTS</b>The karyotype of the fetus was 47,XN,+mar. As detected by STR-QF-PCR, the copy number of GATA178F11 locus on chromosome 18 was 4, and the duplicated fragment was derived from the mother. WGS suggested that the fetus to be 46,XN,dup(18p11.21p11.32).seq [GRCh37/hg19](10 001-15 378 887)× 4, with the duplicated fragment spanning approximately 15.38 Mb.</p><p><b>CONCLUSION</b>The cardiac malformation of the fetus may be attributed to the partial duplication of chromosome 18p. Combined cytogenetic and molecular methods can facilitate prenatal detection of genetic abnormalities.</p>