Browsing by keyword "Face"
Now showing items 1-3 of 3
-
MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in miceMutations in human FYVE, RhoGEF, and PH domain-containing 1 (FGD1) cause faciogenital dysplasia (FGDY; also known as Aarskog syndrome), an X-linked disorder that affects multiple skeletal structures. FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase CDC42. However, the mechanisms by which mutations in FGD1 affect skeletal development are unknown. Here, we describe what we believe to be a novel signaling pathway in osteoblasts initiated by FGD1 that involves the MAP3K mixed-lineage kinase 3 (MLK3). We observed that MLK3 functions downstream of FGD1 to regulate ERK and p38 MAPK, which in turn phosphorylate and activate the master regulator of osteoblast differentiation, Runx2. Mutations in FGD1 found in individuals with FGDY ablated its ability to activate MLK3. Consistent with our description of this pathway and the phenotype of patients with FGD1 mutations, mice with a targeted deletion of Mlk3 displayed multiple skeletal defects, including dental abnormalities, deficient calvarial mineralization, and reduced bone mass. Furthermore, mice with knockin of a mutant Mlk3 allele that is resistant to activation by FGD1/CDC42 displayed similar skeletal defects, demonstrating that activation of MLK3 specifically by FGD1/CDC42 is important for skeletal mineralization. Thus, our results provide a putative biochemical mechanism for the skeletal defects in human FGDY and suggest that modulating MAPK signaling may benefit these patients.
-
Stereophotogrammetry-based facial depth measurements: a novel method for quantifying facial projectionBACKGROUND: Orthognathic surgery leads to alteration of the spatial relationship of the mandible and maxilla resulting changes in the degree of facial projection. Traditional 2-dimensional cephalometry and photographic techniques do not provide data on facial depth. Though stereophotogrammetry can be used as a noninvasive method for evaluating facial depth, the unavailability of ethnicity-specific norms hinder its routine use in clinical practice. The objectives of this study were to (a) generate an analytic scheme suitable for evaluating facial depth using stereophotogrammetry and (b) create normative data for the facial depth measurements for young Hong Kong Chinese adults. METHODS: Stereophotographic images from 41 male and 45 female ethnic Chinese young adults without facial deformities were analyzed. Facial depth measurements were performed based on standard anthropometric landmarks, with the aid of 3dMDVultus software. RESULTS: All facial depth measurements were found in absolute terms to be significantly higher in males. In contrast, the upper face, maxillary, and sublabial depth indices were significantly higher in females, whereas no significant gender differences emerged for lower facial and maxillomandibular indices. CONCLUSIONS: A novel method of using stereophotographic images for quantifying facial depth was evaluated. Normative facial depth measurements for young Hong Kong Chinese adults were established. This gender-specific database can be used as a reference in the diagnosis, treatment planning, or evaluation of outcomes after surgical correction of facial deformities.
-
XK aprosencephaly and anencephaly in sibsRecent studies have suggested a causal and pathogenetic relationship between holoprosencephaly and anencephaly. In support of the proposed relationship we report a sibship that includes anencephalic male twins and a female infant with a severe form of alobar holoprosencephaly, radial aplasia, and oligodactyly. The upper limb and brain malformations are considered to represent aprosencephaly syndrome. The coexistence of anencephaly and aprosencephaly within a sibship suggests that XK aprosencephaly syndrome may be an autosomal recessive disorder.
