Incisor transposition

[Extract] Sir, a 56-year-old male patient reporting for a routine dental check-up revealed right upper central and lateral incisors that had interchanged their positions (Fig. 1). The lateral incisor was slightly malformed (increased mesio-distal and cervico-incisal crown width) and the patient was totally unaware of the condition. An intraoral periapical radiograph revealed transposition of the upper right central and lateral incisors (Fig. 2). An incomplete dens in dente was observed in relation to the lateral incisor. Since the patient was not concerned with aesthetics and because of financial constraints no treatment was instituted

Novel inactivating mutations of the DCAF17 gene in American and Turkish families cause male infertility and female subfertility in the mouse model

PubMedID: 29178422Loss-of-function DCAF17 variants cause hypogonadism, partial alopecia, diabetes mellitus, mental retardation, and deafness with variable clinical presentation. DCAF17 pathogenic variants have been largely reported in the Middle Eastern populations, but the incidence in American families is rare and animal models are lacking. Exome sequencing in 5 women with syndromic hypergonadotropic hypogonadism from 2 unrelated families revealed novel pathogenic variants in the DCAF17 gene. DCAF17 exon 2 (c.127-1G > C) novel homozygous variants were discovered in 4 Turkish siblings, while 1 American was compound heterozygous for 1-stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility. Our results identify 2 novel variants, and show that Dcaf17 plays a significant role in mammalian gonadal development and infertility. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

Molecular Basis for Craniofacial Phenotypes Caused by Sclerostin Deletion

Some genetic disorders are associated with distinctive facial features, which can aid in diagnosis. While considerable advances have been made in identifying causal genes, relatively little progress has been made toward understanding how a particular genotype results in a characteristic craniofacial phenotype. An example is sclerosteosis/van Buchem disease, which is caused by mutations in the Wnt inhibitor sclerostin (SOST). Affected patients have a high bone mass coupled with a distinctive appearance where the mandible is enlarged and the maxilla is foreshortened. Here, mice carrying a null mutation in Sost were analyzed using quantitative micro-computed tomographic (µCT) imaging and histomorphometric analyses to determine the extent to which the size and shape of craniofacial skeleton were altered. Sost-/- mice exhibited a significant increase in appositional bone growth, which increased the height and width of the mandible and reduced the diameters of foramina. In vivo fluorochrome labeling, histology, and immunohistochemical analyses indicated that excessive bone deposition in the premaxillary suture mesenchyme curtailed overall growth, leading to midfacial hypoplasia. The amount of bone extracellular matrix produced by Sost-/- cells was significantly increased; as a consequence, osteoid seams were evident throughout the facial skeleton. Collectively, these analyses revealed a remarkable fidelity between human characteristics of sclerosteosis/van Buchem disease and the Sost-/- phenotype and provide clues into the conserved role for sclerostin signaling in modulating craniofacial morphology