Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.

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(N Engl J Med. 2018;379:464–473) Sequence analysis of cell-free DNA (cfDNA) in screenings for fetal chromosome abnormalities is a success story of modern genomic medicine. In this review, the authors discussed lessons learned from the widespread clinical and biotechnological implementation of this test, ethical and legal concerns, and the future of cfDNA sequencing.

Objective To analyze fetal gene expression at term using umbilical cord blood, in order to provide insights into the effects of maternal obesity on human development. Design Prospective case-control study. Setting Academic tertiary care center. Population Eight obese (BMI ≥ 30) and eight lean (BMI < 25) pregnant women undergoing pre-labor cesarean delivery at term. Methods Women were matched for gestational age and fetal sex. Cord blood RNA was extracted and hybridized to gene expression arrays. Differentially regulated genes were identified using paired t-tests and the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathway Analysis, BioGPS, and Gene Set Enrichment Analysis with a fetal-specific annotation. Z-scores ≥ 2.0 or p-values < 0.01 were considered significant. Main Outcome Measure Functions of differentially regulated genes in fetuses of obese women. Results 701 differentially regulated genes were identified, producing an expression profile implicating neurodegeneration, decreased survival of sensory neurons, and decreased neurogenesis in the fetuses of obese women. Upstream regulators related to inflammatory signaling were significantly activated; those related to insulin receptor signaling, lipid homeostasis, regulation of axonal guidance, and cellular response to oxidative stress were significantly inhibited. Of 26 tissue-specific genes that were differentially regulated in fetuses of obese women, six mapped to the fetal brain. Conclusion Maternal obesity affects fetal gene expression at term, implicating dysregulated brain development, inflammatory and immune signaling, glucose and lipid homeostasis, and oxidative stress. This may have implications for postnatal neurodevelopment and metabolism.

The International Placenta Stem Cell Society (IPLASS) was founded in June 2010. Its goal is to serve as a network for advancing research and clinical applications of stem/progenitor cells isolated from human term placental tissues, including the amnio-chorionic fetal membranes and Wharton's jelly. The commitment of the Society to champion placenta as a stem cell source was realized with the inaugural meeting of IPLASS held in Brescia, Italy, in October 2010. Officially designated as an EMBO-endorsed scientific activity, international experts in the field gathered for a 3-day meeting, which commenced with “Meet with the experts” sessions, IPLASS member and board meetings, and welcome remarks by Dr. Ornella Parolini, President of IPLASS. The evening's highlight was a keynote plenary lecture by Dr. Diana Bianchi. The subsequent scientific program consisted of morning and afternoon oral and poster presentations, followed by social events. Both provided many opportunities for intellectual exchange among the 120 multi-national participants. This allowed a methodical and deliberate evaluation of the status of placental cells in research in regenerative and reparative medicine. The meeting concluded with Dr. Parolini summarizing the meeting's highlights. This further prepared the fertile ground on which to build the promising potential of placental cell research. The second IPLASS meeting will take place in September 2012 in Vienna, Austria. This meeting report summarizes the thought-provoking lectures delivered at the first meeting of IPLASS.

Bi-directional fetomaternal trafficking of cells and nucleic acids during pregnancy is now well established, through the use of molecular techniques including conventional and real-time polymerase chain reaction, as well as fluorescence in situ hybridization. In addition, human leukocyte antigen (HLA) is deposited in the skin of pregnant women. Fetomaternal trafficking is increased in some complications of pregnancy, such as pre-eclampsia, polyhydramnios, polymorphic eruption of pregnancy, preterm labor and specific fetal chromosome aneuploidies. Maternal cells and nucleic acids have been documented in umbilical cord blood and in autopsy tissue of non-transfused neonates. Fetal cells persist postpartum and may be associated with the development of disorders such as scleroderma, lichen planus, lupus and thyroid disease. The extent of fetomaternal trafficking may be affected by three generational HLA relationships. Thus, the consequences of pregnancy extend beyond gestation.

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