Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

De archieven van den etstoei en van de hem opgevolgde collegiën tot 1811 /

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Mededeelingen van den Minister van buitenlandsche zaken aan de staten-generaal ...

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Vergelyking van den republicaenschen met den gregoriaenschen almanach : beginnende van den 1sten Vendemiaire jaer 1 (22 September 1792) dag zyn'er stichtinge, tot den 10 Nivose jaer 14 (laesten December 1805) inclus, tydstip zyn'er vernieting /

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Secrete resolutien van de edele groot mog. heeren Staten van Holland en Westvriesland, genomen zedert den aanvang der bedieninge van den heer Johan de Witt als raad pensionaris van den zelven lande; en door denselfden heer onderscheidentlyk van de Resolutien van consideratie, die op zich zelfs een bysonder werk uitmaken, by een vergadert. Beginnende met den jare 1653, en eindigende met het jare 1668 ...

Titles in red and black; engraved vignette.

De volken van onzen tijd. Bijdragen tot de kennis van den toestand der voornaamste staten in de tweede helft van de negentiende eeuw.

1. Belgie.--2. Groot-Brittaniën.

Bijdrage tot de wordingsgeschiedenis van den grooten oorlog,

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Bijdrage tot de wordingsgeschiedenis van den grooten oorlog /

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Brieven van den nutteloozen toeschouwer,

Brieven van den nutteloozen toeschouwer.--De uren.--De moord op den optimist.--De grootvader.

Eindverslag over de onderzockingen en uitkomsten van den dienst der Rijksopsporing van delfstoffen in Nederland, 1903-1916.

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