Low Expression of LEFTY1 in Placental Villi Is Associated with Early Unexplained Miscarriage.

OBJECTIVE: To investigate the function and underlying mechanism of transforming growth factor­beta (TGF-ß)/bone morphogenetic protein (BMP) signaling pathway in early unexplained miscarriage. STUDY DESIGN: Expression profiles of genes involved in TGF-ß/BMP signaling pathway were compared between placental villous tissue samples from 2 women with missed abortion and those from 2 women with induced abortion by microarray assay. The protein expression level of the most downregulated gene­LEFTY1­was further measured using western blotting in another 8 women with missed abortion and 7 women with induced abortion. RESULTS: A total of 24 genes showed differential expression level between the 2 groups. Their functions were further investigated, of which 6 of 13 upregulated genes were TGF-ß responsive genes. The most reduced gene is LEFTY1, an antagonist of TGF-ß ligand. The protein expression level of LEFTY1 was confirmed to show the same trend as microarray using western blotting. CONCLUSION: A reduced expression of LEFTY1 in women with missed abortion was identified as com-pared with women with induced abortion, which may result in a dysregulation of TGF-ß signaling and may be the underlying mechanism of missed abortion.

[Phenotypic and genetic analysis of a child featuring multiple malformations due to copy number variation on chromosome 5].

OBJECTIVE: To determine the origin of chromosomal aberration for a child featuring multiple malformation, and to correlate the genotype with phenotype. METHODS: Routine G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used for fine mapping of the aberrant region. RESULTS: The karyotype of the child was ascertained as 46,XY. Array CGH has mapped a 14.21 Mb deletion to 5p15.2p15.33, and a very small 3.67 Mb duplication to 5q35.3. The patient has presented features such as mental retardation, heart defect, low-set ears, hypertelorism and down-slanting palpebral fissures. CONCLUSION: Chromosome 5 copy number variation can cause multiple malformation. In contrast to routine karyotype analysis, array CGH can map aberrant region with much higher resolution and accuracy.