Background Pathogenic CDKN1C gain-of-function variants on the maternal allele were initially reported as a cause of IMAGe syndrome characterized by intrauterine growth retardation, metaphyseal dysplasia, primary adrenal insufficiency and genital anomalies. Recently, a maternally inherited CDKN1C missense mutation (p.Arg279Leu) was identified in several members of a single family clinically diagnosed with Silver–Russell syndrome (SRS) but without adrenal insufficiency. Thereafter, two half siblings from UK with familial SRS were described who carried the same mutation. This specific amino acid change is located within a narrow functional region containing the mutations previously associated with IMAGe syndrome. Results Here, we describe a third familial case with maternally inherited SRS due to a missense variant affecting the same amino acid position 279 but leading to a different amino acid substitution (p. (Arg279Ser)). The two affected family members (mother and son) presented with the complete SRS phenotype (both Netchine–Harbison CSS score 5 of 6) but without body asymmetry or adrenal insufficiency. Conclusions In comparison with loss-of-function genomic IGF2 mutations, CDKN1C gain-of-function mutations are a less frequent cause of SRS and seem to affect a cluster of few amino acids.

Endometrial cancer (EC) is a urogenital cancer affecting millions of post-menopausal women, globally. This study aims to identify key miRNAs, target genes, and drug targets associated with EC metastasis. The global miRNA and mRNA expression datasets of endometrial tissue biopsies (24 tumors +3 healthy tissues for mRNA and 18 tumor +4 healthy tissues for miRNAs), were extensively analyzed by mapping of DEGs, DEMi, biological pathway enrichment, miRNA-mRNA networking, drug target identification, and survival curve output for differentially expressed genes. Our results reveal the dysregulated expression of 26 miRNAs and their 66 target genes involved in focal adhesions, p53 signaling pathway, ECM-receptor interaction, Hedgehog signaling pathway, fat digestion and absorption, glioma as well as retinol metabolism involved in cell growth, migration, and proliferation of endometrial cancer cells. The subsequent miRNA-mRNA network and expression status analysis have narrowed down to 2 hub miRNAs (hsa-mir-200a, hsa-mir-429) and 6 hub genes (PTCH1, FOSB, PDGFRA, CCND2, ABL1, ALDH1A1). Further investigations with different systems biology methods have prioritized ALDH1A1, ABL1 and CCND2 as potential genes involved in endometrial cancer metastasis owing to their high mutation load and expression status. Interestingly, overexpression of PTCH1, ABL1 and FOSB genes are reported to be associated with a low survival rate among cancer patients. The upregulated hsa-mir-200a-b is associated with the decreased expression of the PTCH1, CCND2, PDGFRA, FOSB and ABL1 genes in endometrial cancer tissue while hsa-mir-429 is correlated with the decreased expression of the ALDH1A1 gene, besides some antibodies, PROTACs and inhibitory molecules. In conclusion, this study identified key miRNAs (hsa-mir-200a, hsa-mir-429) and target genes ALDH1A1, ABL1 and CCND2 as potential biomarkers for metastatic endometrial cancers from large-scale gene expression data using systems biology approaches.

Recombinant chromosome 8 (Rec8) syndrome (San Luis Valley [SLV] syndrome; OMIM #179613) is a rare chromosome disorder associated with intellectual disability, congenital heart defects, variable skeletal and urogenital anomalies, and dysmorphic features.