MCPH1: A novel case report and a review of the literature

Microcephaly primary hereditary (MCPH) is a congenital disease characterized by nonsyndromic reduction in brain size due to impaired neurogenesis, often associated with a variable degree of intellectual disability (ID). The genetic etiology of MCPH is heterogeneous and comprises more than 20 loci, nearly all following a recessive inheritance pattern. The first causative gene identified, MCPH1 or Microcephalin, encodes a centrosomal protein that modulates chromosome condensation and cell cycle progression. It is also involved in DNA damage response and telomere maintenance in the nucleus. Despite numerous studies on MCPH1 function, MCPH1-affected individuals are rare and the available clinical reports are not sufficient to define the natural history of the disease. Here, we present a novel patient with congenital microcephaly, ID, language delay, short stature, and other minor features such as strabismus. magnetic resonance imaging revealed ventriculomegaly, simplified gyral pattern in the frontal lobes, and a neuronal migration defect. Genetic testing detected a homozygous deletion of exons 1-8 of MCPH1. We compare the patients\u27 characteristics with a list of features from MCPH1 cases described in the literature, in an effort to provide additional clues for a comprehensive definition of disease presentation and evolution

Challenges for the sustainability of university-run biobanks

Most university biobanks begin like other university research projects, i.e. with an idea conceived by an individual researcher in pursuit of his/her own research interests, publications, funding and career. Some biobanks, however, come to have scientific value that goes beyond the projects that were initially responsible for the collection of the samples and data they contain. Such value may derive from inter alia the uniqueness of the samples in terms of their sheer volume, the quality of the samples, the ability to link the samples with information retrieved in disease registries, or the fact that the samples represent very rare diseases. This paper focuses on biobanks of this kind, and the special obligations that publicly funded universities have to ensure the sustainability of biobanks with continued scientific value. We argue that universities should adopt policies to deal with the various, diverse issues which may arise during the lifecycle of a biobank. The policies should be flexible, accommodate the freedoms of individual researchers, and reflect the multifaceted nature of biobanks. Yet they should be specific enough to provide guidance and robust enough to safeguard legal norms and ethical values. The paper sets out concrete recommendations which universities should consider and act upon

CEP128 Localizes to the Subdistal Appendages of the Mother Centriole and Regulates TGF-β/BMP Signaling at the Primary Cilium

Summary: The centrosome is the main microtubule-organizing center in animal cells and comprises a mother and daughter centriole surrounded by pericentriolar material. During formation of primary cilia, the mother centriole transforms into a basal body that templates the ciliary axoneme. Ciliogenesis depends on mother centriole-specific distal appendages, whereas the role of subdistal appendages in ciliary function is unclear. Here, we identify CEP128 as a centriole subdistal appendage protein required for regulating ciliary signaling. Loss of CEP128 did not grossly affect centrosomal or ciliary structure but caused impaired transforming growth factor-β/bone morphogenetic protein (TGF-β/BMP) signaling in zebrafish and at the primary cilium in cultured mammalian cells. This phenotype is likely the result of defective vesicle trafficking at the cilium as ciliary localization of RAB11 was impaired upon loss of CEP128, and quantitative phosphoproteomics revealed that CEP128 loss affects TGF-β1-induced phosphorylation of multiple proteins that regulate cilium-associated vesicle trafficking. : Mönnich et al. show that CEP128 localizes to the subdistal appendages of the mother centriole and basal body of the primary cilium. CEP128 regulates vesicular trafficking and targeting of RAB11 to the primary cilium. CEP128 loss leads to impaired TGF-β/BMP signaling, which, in zebrafish, is associated with defective organ development. Keywords: primary cilium, basal body, centriole, subdistal appendage, centrosome, transforming growth factor β, TGF-β, bone morphogenetic protein, BMP, zebrafish, phosphoproteomics, CEP12