Search results for "chondrodysplasia"
showing 10 items of 35 documents
Skeletal Dysplasia Mutations Effect on Human Filamins’ Structure and Mechanosensing
2016
AbstractCells’ ability to sense mechanical cues in their environment is crucial for fundamental cellular processes, leading defects in mechanosensing to be linked to many diseases. The actin cross-linking protein Filamin has an important role in the conversion of mechanical forces into biochemical signals. Here, we reveal how mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. Employing X-ray crystallography, the structure of these domains was first solved for the human Filamin B. The interaction seen between domains 16 and 17 is broken by shear force as revealed by steered mo…
Unfused Liver Segments: a Case Report of an Unknown Phenotype of the Conradi-Hünermann-Happle Syndrome
2016
Background: Since its description in 1957, Couinaud`s classification of the segmental organization of the liver has remained valid. However, recent investigations by 3-dimensional computed tomography suggest a significant variability of the vascular anatomy and segment volume. Here, we report a surprise finding during the laparoscopic cholecystectomy of a patient with Conradi-Hünermann-Happle syndrome, in whom the liver segments were not fused.
 Case report: Laparoscopic cholecystectomy was performed because of recurrent biliary pancreatitis in a 47 year-old male patient, who had been diagnosed with Conradi-Hünermann-Happle syndrome. Upon direct view, the liver parenchyma appeared norm…
Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia
2006
Skeletal dysplasias are difficult to diagnose for the nonexpert. In a previous study of patients with multiple epiphyseal dysplasia (MED), we identified cartilage oligomeric matrix protein (COMP) mutations in only 36% of cases and suspected that the low-mutation detection rate was partially due to misdiagnosis. We therefore instituted a clinical–radiographic review system, whereby all cases were evaluated by a panel of skeletal dysplasia experts (European Skeletal Dysplasia Network). Only those patients in whom the diagnosis of MED was confirmed by the panel were screened for mutations. Under this regimen the mutation detection rate increased to 81%. When clinical–radiological diagnostic cr…
Recessive multiple epiphyseal dysplasia (rMED): phenotype delineation in eighteen homozygotes for DTDST mutation R279W.
2003
Multiple epiphyseal dysplasia (MED) is a generalised skeletal dysplasia that although relatively mild is associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. In the past, the disorder was subdivided into the milder Ribbing type, usually with flattened epiphyses,1 and the more severe Fairbank type with round epiphyses,2 but many cases were not classifiable as clearly either type.3 MED can be caused by mutations in at least six separate genes: COMP ,4–7 collagen IX ( COL9A1 , COL9A2 , and COL9A3 ),8–13 matrilin 3 ( MATN3 ),15 and the sulphate transporter, DTDST ( DTDST/SLC26A2 ). We have previously repor…
HETEROGENEITY OF METATROPIC DYSPLASIA
1983
Metatropic dysplasia is a neonatally manifest entity that is characterized clinically by a rapidly progressing kyphoscoliosis leading to severe shortening of the originally long trunk ("metatropism"). Major radiographic features include flattening and defective ossification of the vertebral bodies, a narrow thorax and a marked hypoplasia of the basilar portions of the ilia with crescent-shaped iliac crests. There is some evidence of genetic heterogeneity. From five personal observations and from a review of the literature we conclude that metatropic dysplasia comprises at least three genetic entities: (1) a nonlethal type with autosomal recessive transmission; (2) a nonlethal dominant type …
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
2000
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated p…
Chondrodysplasia punctata — Rhizomelic form
1976
Pathologic, ultrastructural and radiologic studies are described on 3 infants with the rhizomelic form of chondrodysplasia punctata. Radiologic criteria in the young infant include radiolucent coronal clefts dividing all or most of the thoracic and lumbar vertebral bodies, short humeri with flared metaphyses and punctate calcifications commonly present adjacent to the ossified ischial and pubic bones and less commonly in other locations. In late infancy and childhood the radiologic criteria include demineralization in all bones with slow maturation, flat vertebral bodies, short humeri and femora, metaphyseal flaring, especially in the distal humerus, proximal femur and proximal tibia, immat…
Profilin 1 is required for abscission during late cytokinesis of chondrocytes
2009
Profilins are key factors for dynamic rearrangements of the actin cytoskeleton. However, the functions of profilins in differentiated mammalian cells are uncertain because profilin deficiency is early embryonic lethal for higher eukaryotes. To examine profilin function in chondrocytes, we disrupted the profilin 1 gene in cartilage (Col2pfn1). Homozygous Col2pfn1 mice develop progressive chondrodysplasia caused by disorganization of the growth plate and defective chondrocyte cytokinesis, indicated by the appearance of binucleated cells. Surprisingly, Col2pfn1 chondrocytes assemble and contract actomyosin rings normally during cell division; however, they display defects during late cytokines…
Mutation Analysis of Core Binding Factor A1 in Patients with Cleidocranial Dysplasia
1999
SummaryCleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature, supernumerary teeth, and other skeletal anomalies. We recently demonstrated that mutations in the transcription factor CBFA1, on chromosome 6p21, are associated with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. In 18 patients, mutations were detected in the coding region of the CBFA1 gene, including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies this residue as crucial for CBFA1 function. …
A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia
2000
Winterpacht, Andreas, Katja Hilbert, Christiane Stelzer, Thorsten Schweikardt, Heinz Decker, Hugo Segerer, Jürgen Spranger, and Bernhard Zabel. A novel mutation in FGFR-3 disrupts a putative N-glycosylation site and results in hypochondroplasia. Physiol. Genomics 2: 9–12, 2000.—Fibroblast growth factor receptor 3 (FGFR3) is a glycoprotein that belongs to the family of tyrosine kinase receptors. Specific mutations in the FGFR3 gene are associated with autosomal dominant human skeletal disorders such as hypochondroplasia, achondroplasia, and thanatophoric dysplasia. Hypochondroplasia (HCH), the mildest form of this group of short-limbed dwarfism disorders, results in ∼60% of cases from a mut…