ABSTRACT
INTRODUCTION: Breastfeeding offers the optimal feeding option for newborns in terms of nutritional content and reinforces mother-infant bonding. As a physiological process intrinsically linked to parturition, breastfeeding is no longer reserved for puerperal mothers. Progress in understanding the intricacies of lactogenesis and breastfeeding has further paved the way for artificially induced lactation in recent years. MAIN ISSUES: We describe the case of a mother through surrogacy with XY karyotype and complete androgen insensitivity syndrome who wished to breastfeed her child. MANAGEMENT: Through a combination of estrogen therapy, galactagogues, and mechanical breast stimulation she was able to partially breastfeed her child for one month. CONCLUSION: This case further shifts the concept that breastfeeding is a physiological process confined to only puerperal mothers and offers an opportunity to a wider group of nontraditional mothers to take part in the unique experience of breastfeeding.
Subject(s)
Androgen-Insensitivity Syndrome/drug therapy , Lactation/drug effects , Mothers , Adult , Breast Feeding/methods , Estrogen Receptor Modulators/pharmacology , Estrogen Receptor Modulators/therapeutic use , Estrogens/pharmacology , Estrogens/therapeutic use , Female , Galactogogues/pharmacology , Galactogogues/therapeutic use , Humans , Lactation/physiology , Male , Treatment OutcomeABSTRACT
Low-grade gliomas (LGGs) account for about a third of all brain tumours in children. We conducted a detailed study of DNA methylation and gene expression to improve our understanding of the biology of pilocytic and diffuse astrocytomas. Pilocytic astrocytomas were found to have a distinctive signature at 315 CpG sites, of which 312 were hypomethylated and 3 were hypermethylated. Genomic analysis revealed that 182 of these sites are within annotated enhancers. The signature was not present in diffuse astrocytomas, or in published profiles of other brain tumours and normal brain tissue. The AP-1 transcription factor was predicted to bind within 200 bp of a subset of the 315 differentially methylated CpG sites; the AP-1 factors, FOS and FOSL1 were found to be up-regulated in pilocytic astrocytomas. We also analysed splice variants of the AP-1 target gene, CCND1, which encodes cell cycle regulator cyclin D1. CCND1a was found to be highly expressed in both pilocytic and diffuse astrocytomas, but diffuse astrocytomas have far higher expression of the oncogenic variant, CCND1b. These findings highlight novel genetic and epigenetic differences between pilocytic and diffuse astrocytoma, in addition to well-described alterations involving BRAF, MYB and FGFR1.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , DNA Methylation , Adolescent , Adult , Astrocytoma/metabolism , Astrocytoma/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Brain/metabolism , Brain/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Child , Child, Preschool , CpG Islands , Cyclin D1/genetics , Cyclin D1/metabolism , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Neoplasm Grading , Promoter Regions, Genetic , Transcription Factor AP-1/metabolism , Young AdultABSTRACT
Genomic structural variation, which can be defined as differences in the copy number, orientation, or location of relatively large DNA segments, is not only crucial in evolution, but also gives rise to genomic disorders. Whereas the major mechanisms that generate structural variation have been well characterised, insights into additional mechanisms are emerging from the identification of short regions of DNA sequence homology, also known as microhomology, at chromosomal breakpoints. In addition, functional studies are elucidating the characteristics of microhomology-mediated pathways, which are mutagenic. Here, we describe the features and mechanistic models of microhomology-mediated events, discuss their physiological and pathological significance, and highlight recent advances in this rapidly evolving field of research.
