Hippocampal radial glial subtypes and their neurogenic potential in human fetuses and healthy and Alzheimer's disease adults

Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX+ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin+ and/or GFAPδ+ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult. Key words: adult neurogenesis, hippocampus, human fetal brain, neurogenesis, radial glial cell

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.We are indebted to all families for participating in this study. We would like to acknowledge Dr. Natasha Laidlew, who initially suggested the diagnosis in one of the cases and provided important phenotypic information, and Dr. María-Luisa Martínez-Fernández for the critical management of biosamples in ECEMC Program of Spain. Financial assistance was received in support of the study by grants from the German Federal Ministry of Education and Research (BMBF) (GeNeRARe, FKZ: 01GM1519D) to M. Z. and from the Institute of Health Carlos III: Convenio ISCIII-ASEREMAC, and Fundación 1000 sobre Defectos Congénitos, of Spain to E. B.-S. and I. R. G.S

Growth Restriction, Osteopenia, Placental Massive Perivillous Fibrin Deposition With (or Without) Intervillous Histiocytes and Renal Tubular Dysgenesis—An Emerging Complex

We describe a case of a pregnancy complicated by early onset asymmetric growth restriction with anhydramnios with termination occurring at 21 weeks. Fetal autopsy showed demineralization of bones and renal tubular dysgenesis. Placental pathology showed features of massive perivillous fibrin deposition and chronic histiocytic intervillositis. We review prior documentation of this association and briefly discuss potential pathogenesis

Case report: Antenatal diagnostic of a polymalformative syndrome due to biallelic BRCA2 mutations

International audienceTesting the partner of a BRCA2 carrier must always be discussed. If both members of the couple are BRCA2 carriers, they should be informed about the high risks of polymalformative syndromes

Severe Phenotype of Cutis Laxa Type 1B with Antenatal Signs due to a Novel Homozygous Nonsense Mutation in <b><i>EFEMP2</i></b>

Abstract: EFEMP2 mutations are known to be responsible for autosomal recessive cutis laxa type 1B (ARCL1B), a rare multisystem disease affecting skin, skeleton, and vascular structures. We report 2 additional related cases of ARCL1B of particular severity leading to termination of pregnancy. Cardinal signs of this connective tissue disease were already seen during the second trimester of pregnancy, then confirmed and clarified at autopsy. Anomalies included cutis laxa, arachnodactyly, clubfoot, wormian bones, moderate bowing of long bones with slender bone trabeculae, rib fractures, undermuscularized diaphragm, hiatal hernia, and arterial tortuosity with thick vascular walls and disorganized elastic fibers. Sequencing of the EFEMP2 gene revealed a novel homozygous nonsense mutation: c.639C>A (p.Cys213*). We performed a thorough histological analysis and discuss differential diagnoses, genotype-phenotype correlations, and the challenge of prenatal diagnosis of this disease. (c) 2018 S. Karger AG, Base