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Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Differential diagnosis:Treacher Collins syndrome: mandibulofacial dysostosis (MFD), coloboma of the lower eyelid with deficient eyelashes, normal limbs, very rare extracranial malformations caused by dominant mutations in TCOF1. Miller syndrome: MFD associated with postaxial limb defects. Mutations in the gene DHODH have been identified: autosomal recessive. Acrofacial dysostosis, Nager type (p. 418). Townes-Brocks syndrome: triad consisting of imperforate anus, dysplastic ears with or without preau-ricular tags (possibly associated with hearing impairment) and thumb malformations (triphalangeal, duplicated, hypoplastic). Associated features can include genitourinary malformations, congenital heart disease, foot malformations. Mental retardation is not common. Caused by dominant mutations in SALL1. Branchio-oto-renal (BOR) syndrome: facial asymmetry or facial palsy are variable features, branchial cleft sinus or fistula on the neck, malformations of ear structures (outer, middle and inner) cause conductive, sensorineural or mixed hearing loss, renal malformations. Autosomal dominant, there is genetic heterogeneity and three genes are known, EYA1, SIX5 and SIX1. VACTERL association (p. 590); MURCS association: uterine aplasia/hypoplasia, renal agenesis/ectopia, abnormal cervical or upper thoracic vertebrae, abnormal ribs, Sprengel shoulder, upper limb abnormalities and deafness.
Bioengineering strategies for nephrologists: kidney was not built in a day
Published in Expert Opinion on Biological Therapy, 2020
Anna Julie Peired, Benedetta Mazzinghi, Letizia De Chiara, Francesco Guzzi, Laura Lasagni, Paola Romagnani, Elena Lazzeri
The blastocyst complementation is a technique originally developed by Chen et al. in 1993 [33] to assay gene function in lymphocyte development. It consists in injecting embryonic stem cells (ESCs) into blastocysts, the initial embryonic stage following fertilization, and to transfer the embryo into the uteri of a foster mother. It has been applied to a wide range of tissues over the years, including thymic epithelia [34], heart [35], germ cells [36], hepatocytes [37] pancreas [38] and lungs [39]. Usui and colleagues used this system to compensate for the developmental defect of the Sall1−/- mice, in which kidneys do not form [40]. Sall1 is expressed during embryonic development in epithelial cellular lineages originating from the metanephric mesenchyme and renal stroma, and mice deficient for Sall1 die right after birth from kidney agenesis. The authors injected wild type murine ESCs or induced pluripotent stem cells (iPSCs) into blastocysts form Sall1−/- mice and observed the bilateral formation of kidneys entirely formed by the injected pluripotent stem cell (PSC)-derived cells, with the exception of structures that do not depend on Sall1 expression to develop, such as collecting ducts from ureteric buds and microvascular endothelial cells. This proof-of-principle study shows that this technique could be used to generate donor PSCs-derived kidneys, but that in order to generate an entire organ from PSCs-derived cells all renal lineages must be absent from the blastocyst.
Regenerating the kidney using human pluripotent stem cells and renal progenitors
Published in Expert Opinion on Biological Therapy, 2018
Francesca Becherucci, Benedetta Mazzinghi, Marco Allinovi, Maria Lucia Angelotti, Paola Romagnani
In the very first experiment, wild-type mouse pluripotent SCs were injected into Sall1 knockout mouse blastocysts in which kidneys did not developed because of the genetic defect [79]. This led to the generation of kidneys entirely formed by the injected mouse-derived cells, except for structures not under the influence of Sall1 expression (such as collecting ducts and microvasculature), thus rescuing bilateral renal agenesis [79]. Unfortunately, the resulting chimeric animals did not survive until adulthood for reasons that are not completely clear [79]. Following the first experiments performed in rodents, the research shifted to generate chimeric animals between human pluripotent SCs and larger animals (e.g. pigs), in order to obtain organs sized as closer as possible to that of humans. To this aim, the potential of human pluripotent SCs to survive into the blastocyst of pigs and cattle has been tested and gave very preliminary but promising results [82]. Obviously, more studies are needed to set up the experimental conditions that are proper to the scope of generating xeno-kidneys suitable for kidney replacement purposes.
SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts
Published in OncoImmunology, 2018
Marie Kroemer, Laurie Spehner, Patricia Mercier-Letondal, Laura Boullerot, Stefano Kim, Marine Jary, Jeanne Galaine, Emilie Picard, Christophe Ferrand, Thierry Nguyen, Fabrice Larosa, Olivier Adotévi, Yann Godet, Christophe Borg
Spalt (sal) genes were first identified in Drosophila melanogaster in which they have important roles in homeotic specifications.1,2 In human, homologue spalt genes, so called Sal Like (SALL), are split up in four paralogue groups, SALL1, SALL2, SALL3 and SALL4.3 SALL4 encodes a C2 H2 zinc finger transcription factor of unusual but characteristic structure.4 In adult, a major role of SALL4 protein is to regulate hematopoiesis by conferring to hematopoietic stem cells their capacity of self-renewal and pluripotency.5,6 Furthermore, SALL4 protein can be detected in spermatogonial, adipose and embryonic stem cells during early development.7