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Journal of Medical Genetics Oct 2002Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental...
Dyggve-Melchior-Clausen syndrome (DMC) is an autosomal recessive condition characterised by short trunk dwarfism, scoliosis, microcephaly, coarse facies, mental retardation, and characteristic radiological features. X rays show platyspondyly with double vertebral hump, epiphyseal dysplasia, irregular metaphyses, and a characteristic lacy appearance of the iliac crests. Electron microscopy of chondrocytes have shown widened cisternae of rough endoplasmic reticulum and biochemical analyses have shown accumulation of glucosaminoglycan in cartilage, but the pathogenesis of DMC remains unexplained. Here, we report on the homozygosity mapping of a DMC gene to chromosome 18q21.1 in seven inbred families (Zmax=9.65 at theta=0 at locus D18S1126) in the genetic interval (1.8 cM) defined by loci D18S455 and D18S363. Despite the various geographical origins of the families reported here (Morocco, Tunisia, Portugal, and Lebanon), this condition was genetically homogeneous in our series. Continuing studies will hopefully lead to the identification of the disease causing gene.
Topics: Abnormalities, Multiple; Bone Diseases, Developmental; Child; Child, Preschool; Chromosomes, Human, Pair 18; Consanguinity; Dwarfism; Female; Genetic Markers; Haplotypes; Homozygote; Humans; Intellectual Disability; Limb Deformities, Congenital; Loss of Heterozygosity; Male; Pedigree; Pelvis; Physical Chromosome Mapping; Radiography; Scoliosis; Syndrome
PubMed: 12362026
DOI: 10.1136/jmg.39.10.714 -
Pediatric Radiology Nov 2000The aim of this study was to assess physeal fractures of the pediatric knee identified by MR imaging and to describe the MR findings of such fractures. The authors...
The aim of this study was to assess physeal fractures of the pediatric knee identified by MR imaging and to describe the MR findings of such fractures. The authors reviewed 315 consecutive pediatric knee MR examinations done to assess for traumatic injury. The MR images were reviewed for evidence of physeal fracture. Fractures were classified by the Salter-Harris system, and associated findings and injuries were noted. Plain radiographs and medical records were reviewed. Seven distal femoral physeal fractures (Salter II, n = 6; Salter III, n = 1) and two proximal tibia physeal fractures (Salter III, n = 1; complex Salter IV, n = 1) were identified. Magnetic resonance demonstrated widening of a portion of the physis with visualization of a metaphyseal/epiphyseal fracture line. Periosteal elevation was observed in six cases. Four patients had associated ligamentous or meniscal injuries. Plain radiographs were available for review in eight patients. Bone abnormalities suggesting fracture were evident in six of eight patients; however, the fracture was fully delineated in only one patient. The diagnosis or confirmation of fracture by MR changed clinical management in seven of eight patients in whom follow-up was available. Physeal fractures of the pediatric knee are occasionally diagnosed by MR. Magnetic resonance provides improved delineation of non-displaced physeal fractures of the knee, while simultaneously allowing for evaluation of soft tissue structures.
Topics: Adolescent; Child; Epiphyses; Female; Femoral Fractures; Humans; Knee Injuries; Magnetic Resonance Imaging; Male; Tibial Fractures
PubMed: 11100491
DOI: 10.1007/s002470000319 -
Endocrine Journal Aug 1997Jansen-type metaphyseal chondrodysplasia (JMC) has both delayed ossification in long bones and usually hypercalcemia. We report a Japanese male patient with JMC who...
Jansen-type metaphyseal chondrodysplasia (JMC) has both delayed ossification in long bones and usually hypercalcemia. We report a Japanese male patient with JMC who presented with rachitic signs on radiographs, hypercalcemia (13 mg/dl) and low %TRP at age 3 months (mo). Hypercalcemia was treated from age 3 mo to 11 yr. Progressive widening, splaying and fragmentation of the metaphyses have been recognized on radiographs which resulted in shortened tubular bones and consequent short stature [107 cm (-6.5 SD)] at age 13 yr. Hypercalcemia tended to normalize, and %TRP became normal at age 13 yr. Repeated measurements of serum PTH and PTH-related protein (PTHrP) levels showed that they were low or normal in the face of hypercalcemia and high urine cAMP excretion, which led us to suspect constitutive activation of the PTH/PTHrP receptor. Direct sequencing of PTH/PTHrP receptor complementary DNA from skin fibroblast cells revealed a CAC to CGC transversion yielding a strictly conserved His223 to Arg substitution found in 90% of DNA fragment in the second transmembrane domain of the receptor. This mutation created a restriction site Sphl (G/CATG/C). Direct sequencing of genomic DNA and also restriction enzyme digestion revealed heterozygous transition. The mutation was absent in the parents with normal phenotype. We conclude that both dysplastic bone lesions and calcium homeostasis are age-dependent in JMC, and that the His223-Arg substitution is the same as that found in four Caucasian patients with a similar phenotype irrespective of the ethnic difference, and that the preferential expression of an abnormal allele of the PTH/PTHrP receptor mRNA in skin fibroblast despite heterogygotic transversion in the genomic DNA suggests the importance of allele expression.
Topics: Dwarfism; Humans; Infant, Newborn; Male; Osteochondrodysplasias; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Polymerase Chain Reaction; Proteins; RNA, Messenger; RNA-Directed DNA Polymerase; Receptors, Parathyroid Hormone; Sequence Analysis, DNA
PubMed: 9447281
DOI: 10.1507/endocrj.44.493 -
Journal of Medical Genetics Mar 1996The features of a child with osteogenesis imperfecta type III (OI III) resulting from the heterozygous substitution of glycine 1006 by alanine in the pro alpha 2(I)...
Arachnoid cyst and chronic subdural haematoma in a child with osteogenesis imperfecta type III resulting from the substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen.
The features of a child with osteogenesis imperfecta type III (OI III) resulting from the heterozygous substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen were studied. He was born at term with the clinical features of severe OI, including deep grey-blue sclerae. He had severe osteopenia and all long bones were smaller than normal with cortical thinning, metaphyseal expansion, poor metaphyseal modelling, and multiple fractures. However, the vertebrae, pelvis, and shoulder girdle were of normal shape and there were few rib fractures. Histological examination of the calvarium and tibial shaft showed woven bone without lamellar bone or Haversian systems. The shafts of the long bones were widened owing to repeated fractures. Progressive enlargement of the calvarium occurred between 3 and 4.5 months of age owing to bilateral chronic subdural haematomata and a large arachnoid cyst in the Sylvian fissure. The cyst was probably developmental in origin while the subdural collections were probably the result of perinatal skull trauma. The cyst and the subdural collections resolved following drainage but ventricular dilatation with normal cerebrospinal fluid pressure followed. The proband is the first reported case of OI with a glycine substitution by alanine in the pro alpha 2(I) chain of type I procollagen.
Topics: Adult; Alanine; Arachnoid Cysts; Female; Genetic Carrier Screening; Glycine; Hematoma, Subdural; Humans; Infant; Male; Osteogenesis Imperfecta; Point Mutation; Procollagen; Skull; Tomography, X-Ray Computed
PubMed: 8728690
DOI: 10.1136/jmg.33.3.193 -
Poultry Science Nov 1980Broiler chicks fed corn-soy rations supplemented with toxic levels of magnesium from one day of age grew poorly, developed diarrhea, and exhibited characteristic...
Broiler chicks fed corn-soy rations supplemented with toxic levels of magnesium from one day of age grew poorly, developed diarrhea, and exhibited characteristic skeletal abnormalities. Tibiae from magnesium intoxicated chicks were shortened, thickened, and bowed. Percent tibial ash was greatly reduced. Upon microscopic examination, the bone lesion appeared rachitic as evidenced by widened and lengthened growth plates, excessive osteoid seams on endochandral bone, and osteoid or bone capped metaphyseal blood vessels with very few associated osteoblasts. Tibial calcium to phosphorus mass ratios decreased while tibial magnesium to phosphorus mass ratios increased concomitantly with increased dietary magnesium. Calcium and phosphorus homeostasis was possibly affected as evidenced by a general decrease in size and cellularity of parathyroid glands and a general increase in size and cellularity of ultimobranchial glands.
Topics: Animals; Bone Diseases; Chickens; Magnesium; Parathyroid Diseases; Poultry Diseases; Tibia; Ultimobranchial Body
PubMed: 7465508
DOI: 10.3382/ps.0592403