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The present study described the diagnosis of a fetus with sex chromosome mosaicism in three cell lines and two marker chromosomes. A 24‑year‑old woman underwent amniocentesis at 21 weeks and 4 days of gestation due to noninvasive prenatal testing identifying that the fetus had sex chromosome abnormalities. Amniotic cell culture revealed a karyotype of 45,X[13]/46,X,+mar1[6]/46,X,+mar2[9], and prenatal ultrasound was unremarkable. The woman underwent repeat amniocentesis at 23 weeks and 4 days of gestation for molecular detection. Single nucleotide polymorphism (SNP) microarray analysis on uncultured amniocytes revealed that the fetus had two Y chromosomes and 7.8‑Mb deletions in Yq11.222q12. The deletion regions included DAZ, RBMY and PRY genes, which could cause spermatogenesis obstacle and sterility. Interphase fluorescence in situ hybridization (FISH) using centromeric probes DXZ1/DYZ3/D18Z1 was performed on uncultured amniocytes to verify the two marker chromosomes to be Y chromosome derivatives. According to these examinations, the mar1 was identified as a derivative of the Y chromosome with a deletion in Yq11.222q12, and the mar2 was identified as a dicentric derivative of the Y chromosome. The molecular karyotype was therefore 45,X,ish(DXZ1+, DYZ3‑,D18Z1++)[5]/46,X,del(Y)(q11.222),ish(DXZ1+,DYZ3+,D18Z1++)[11]/46, X,idic(Y)(q11.222),ish(DXZ1+,DYZ3++,D18Z1++)[14]. The comprehensive use of cytogenetic, SNP array and FISH detections was advantageous for accurately identifying the karyotype, identifying the origin of the marker chromosome and preparing effective genetic counseling.

Background: Cenani‐Lenzsyndactyly syndrome (CLSS; OMIM 212780) is a rare autosomal recessive acral deformity, which is mainly manifested in the fusion of fingers or toes, disordered phalangeal structure, shortening or fusion of the radius and ulna, and renal hypoplasia. Case presentation: Our report described an individual with mild phenotypes from China. His parents were not consanguineous. The affected individual was non‐dysmorphic. Standard X‐ray showed that the both hands have only four metacarpal bones. The distal end of the first metacarpal bone on the right was relatively slender, and the distal phalanx was absent. Multiple phalanges and some soft tissues of both hands were fused. Exome sequencing revealed a novel biallelic c.282C⟩Avariant in low‐density lipoprotein receptor‐related protein 4 (LRP4; OMIM604270; NM_002334.4) causing p. (Asn94Lys) change in the encoded protein. This variant is predicted to be potentially pathogenic, affecting protein structure and function. Conclusion: We report a novel missense variant present in homozygosity in LRP4 to broaden the pathogenic spectrum of LRP4 in syndactyly, and exome sequencing technology is a powerful tool for genetic analysis in prenatal diagnosis and medical research, as a preferred method for the diagnosis of syndactyly and related phenotypes. [ABSTRACT FROM AUTHOR]

Background: Our aim was to evaluate the clinical utility of non-invasive prenatal testing for pregnant women with different diagnostic indications. Methods: In eight counties and districts of Yancheng, we studied 13,149 pregnant women with different indications who were offered NIPT for fetal screening, including for sex chromosomal aneuploidies (SCAs), rare autosomal trisomies (RATs), and subchromosomal copy number variations (CNVs). The purpose was to compare the detection of positive predictive values (PPVs) of different indications with the use of NIPT. The results were validated by karyotyping, chromosomal microarray analysis (CMA), or follow-up of pregnancy outcomes. Results: 13,149 maternal plasma samples were sequenced, among which 28 samples (0.2%) failed the sequencing quality control. The remaining 13,121 samples were analyzed, and birth follow-up missed 2,192 samples (16.7%). The PPVs of NIPT results for trisomy 21 (T21) and trisomy 18 (T18) and SCAs were 96.67, 63.64, and 31.34%, respectively. Among the advanced maternal age (AMA), serum screening high risk (SSHR), serum screening intermediate risk (SSIR), and voluntary screening (VS) groups, the PPVs for the common trisomies were 81.25, 85.71, 100, and 70%, respectively; the PPVs for total chromosomal abnormalities were 55.82, 65.22, 23.08, and 36.59%, respectively. Conclusion: NIPT for T21 and T18 and SCAs screening were ideal, and the PPVs for trisomy 13 (T13), RATs, and CNVs were low. For the AMA and VS groups, NIPT could be used as a first-line screening program; for SSHR and SSIR groups, NIPT could be used as a second-line supplementary screening program. [ABSTRACT FROM AUTHOR]