Osteogenesis imperfecta lethal in infancy: Case report and scanning electron microscopic studies of the deciduous teeth

Radiologic evaluation of the skeleton and scanning electron microscopic studies of the teeth were performed on an infant boy with a lethal osteogenesis imperfecta (OI) syndrome who died at 10 mo of pneumonia. The skeletal findings included ribs that were focally expanded by fracture calluses, flat vertebral bodies, and wide limb bones. On fractured tooth surfaces, the enamel and dentin were normal as was the dentin calcification front. Although microscopic abnormalities have been noted in teeth from previously reported infants with lethal OI, a few studies also report infants with normal teeth. These differences in dental findings may indicate heterogeneity in OI lethal in infancy. Results of our study indicate that, until the primary biochemical defects in the OI syndromes are elucidated, examination of teeth from other infants with lethal OI and detailed evaluation of other clinical and skeletal features will aid in delineating heterogeneity and variation in expression in lethal OI.     

Scanning microscopy of platypus teeth

Summary Anorganic unerupted developing teeth and airdired erupted teeth of the platypus (Ornithorhynchus anatinus) were examined in a scanning electron microscope and in a tandem scanning reflected light microscope. Typically mammalian developing fronts of enamel and dentine were identified in the anorganic unerupted specimens. The developing teeth were particularly small and fragile and the enamel elusive and difficult to examine in the normal way for morphological detail. Prepared fractured surfaces of unerupted specimens revealed preferentially oriented crystallite groups in the enamel generally perpendicular to the developing front and a highly globular, mineralized pattern in the dentine with fine diameter, sparsely distributed dentinal tubules.Although optically homogeneous, the enamel of both developing and mature teeth displayed well-defined incremental lines, radial clefts, crystallite domains of variable size and outline, and fine tubules when examined by high contrast, back-scattered electron imaging. The enamel is prismatic only in part; well-formed, regular prisms not being a primary feature of platypus enamel. This can be related to the variability inherent in the developing surface and the thinness of the enamel layer. No surface was found which could be confidently identified as cementum; those developing surfaces not covered by enamel displaying small calcospherites which elsewhere marked the outer aspect of the dentine.     

Genetic heterogeneity in osteogenesis imperfecta.

An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile conductive hearing loss. A second group, who comprised the majority of newborns with neonatal fractures, all died before or soon after birth. These had characteristic broad, crumpled femora and beaded ribs in skeletal x-rays. Autosomal recessive inheritance was likely for some, if not all, of these cases. A third group, two thirds of whom had fractures at birth, showed severe progressive deformity of limbs and spine. The density of scleral blueness appeared less than that seen in the first group of patients and approximated that seen in normal children and adults. Moreover, the blueness appeared to decrease with age. All patients in this group were sporadic cases. The mode of inheritance was not resolved by the study, but it is likely that the group is heterogeneous with both dominant and recessive genotypes responsible for the syndrome. The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.     

Odontoblast Dysfunction in Osteogenesis Imperfecta: An LM,SEM, and Ultrastructural Study

The inherited dentin defect dentinogenesis imperfecta (DI), while clinically obvious in osteogenesis imperfecta (OI) Types IB and IC, II, III, and IVB, is now thought to be present in all children with OI, in a continuum from minimal to severe dentin pathology. This collaborative study further clarifies the structural and ultrastructural dentin changes in the teeth of OI children with clinically obvious DI, and attempts to explain these in terms of odontoblast dysfunction. Collaborative studies were carried out in Melbourne, Australia, and Strasbourg, France, using light and polarized-light microscopy, scanning and transmission electron microscopy (SEM, TEM), selected-area diffraction (SAD), and x-ray spectroscopy (EDX). These showed structurally normal enamel (but containing long and broad lamellae) and a normally scalloped dentino-enamel junction (DEJ), but severe pathologic changes in the dentin. An initial narrow band of normal-appearing dentin tubules (including the mantle layer) ceased abruptly and was replaced by a wavelike laminar zone parallel to the DEJ with occluded tubules. Multiple parallel channels of 5-10 &#119 m diameter were present at right angles to the DEJ indenting this zone, some terminating in retro-curved "processes." The abnormal dentin containing these channels almost completely occluded the pulp chamber. The structural and ultrastructural changes seen can be explained on the basis of the collagen defect in OI resulting in odontoblast dysfunction, which produces a distinct phenotype and one that is different from that in bone.     

Odontoblast dysfunction in osteogenesis imperfecta: an LM,SEM, and ultrastructural study

The inherited dentin defect dentinogenesis imperfecta (DI), while clinically obvious in osteogenesis imperfecta (OI) Types IB and IC, II, III, and IVB, is now thought to be present in all children with OI, in a continuum from minimal to severe dentin pathology. This collaborative study further clarifies the structural and ultrastructural dentin changes in the teeth of OI children with clinically obvious DI, and attempts to explain these in terms of odontoblast dysfunction. Collaborative studies were carried out in Melbourne, Australia, and Strasbourg, France, using light and polarized-light microscopy, scanning and transmission electron microscopy (SEM, TEM), selected-area diffraction (SAD), and x-ray spectroscopy (EDX). These showed structurally normal enamel (but containing long and broad lamellae) and a normally scalloped dentino-enamel junction (DEJ), but severe pathologic changes in the dentin. An initial narrow band of normal-appearing dentin tubules (including the mantle layer) ceased abruptly and was replaced by a wavelike laminar zone parallel to the DEJ with occluded tubules. Multiple parallel channels of 5-10 microns diameter were present at right angles to the DEJ indenting this zone, some terminating in retro-curved "processes." The abnormal dentin containing these channels almost completely occluded the pulp chamber. The structural and ultrastructural changes seen can be explained on the basis of the collagen defect in OI resulting in odontoblast dysfunction, which produces a distinct phenotype and one that is different from that in bone.     

Confocal microscopy of dentinal tubules in human tooth stained with alizarin red

 The present study was designed to analyze the structures of dentinal tubules by confocal microscopy. Undecalcified ground sections of human teeth were stained with alizarin red in 0.1% KOH aqueous solution, and examined by confocal microscopy. Alizarin red stained dentinal tubules, interglobular dentine, granular layer of Tomes, and the surface of dentine. Interglobular dentine was seen between the outer and middle layers of coronal dentine. At the outer layer of coronal dentine, the dentinal tubules were thin and showed numerous branches. At the middle layer of coronal dentine, dentinal tubules displayed two types. The type I tubules are the dentinal tubules that do not show any nodular structures and the type II tubules are the dentinal tubules that appear bamboo-like with many nodules. In the cross section through the type II tubules, the nodules appeared as fine circular tubules surrounding the dentinal tubules. The circular tubules of nodules adhered to one side of the dentinal tubules. When the fluorescence images were compared with the images taken by transmission light mode, the fluorescence of dentinal tubules was seen at the inner surface of dentinal tubules, and the fluorescence of nodules was seen at interface between peritubular and intertubular dentine. Most of the dentinal tubules were of the type II tubules in the teeth from older individuals, whereas the type II tubules were scarce in the teeth from younger individuals. At the inner layer of coronal dentine, the dentinal tubules have no nodules and branches were scarce. The dentinal tubules of radicular dentine were different from those of coronal dentine. Most of the dentinal tubules were the type I tubules. Numerous fine branches were seen at the outer and middle layers of radicular dentine. No interglobular dentine was seen in the root except at the cervical part, and the granular layer of Tomes was also positive with alizarin red. At the cervical part of the root, interglobular dentine was present and the dentinal tubules displayed types I and II. Accepted: 19 August 1998     

A family with homozygous and heterozygous p.Gly337Ser mutations in COL1A2

Osteogenesis imperfecta (OI) is commonly caused by monoallelic mutations in COL1A1 or COL1A2. Biallelic mutations are extremely rare. Only five previous reports have identified seven OI patients with homozygous mutations in COL1A2. OI is a genetically and phenotypically heterogeneous disorder which challenges an establishment of genotype-phenotype correlation. Notably, more than thirty patients with OI possess the heterozygous mutation, p.Gly337Ser, in COL1A2. Their clinical severity ranges from mild OI type I to severe types III and IV. Here, we report a 17-year-old Thai female with recurrent bone fractures, short stature, blue sclerae, triangular face, missing teeth, dentinogenesis imperfecta (DI), skeletal deformities, and scoliosis. She was diagnosed with OI type III. Her parents were second-cousin-once-removed. The father was a professional Thai boxer. Both had normal bone mineral density, no history of bone fractures, and only teeth problems. They were diagnosed with DI without OI. Whole exome sequencing identified that the proband harbored the homozygous mutation, c.1009G > A (p.Gly337Ser), in exon 19 of COL1A2 while her parents were heterozygous for this mutation. This study reports the eighth child with OI and the homozygous mutation in COL1A2; and the first two individuals with the heterozygous p.Gly337Ser mutation in COL1A2 causing an isolated DI without OI.     

Fine structure of the agranular cytoplasmic tubules in the lamprey chloride cells

The chloride cells of the lamprey, Lampetra japonica, have been studied by electron microscopy. The most characteristic feature of the chloride cells in lamprey is that the cytoplasm is filled with a large number of mitochondria and numerous agranular cytoplasmic tubules arranged as bundles or as branched reticular networks. These tubules are frequently continuous with the plasma membrane. They are also characterized by a coating on the cisternal surfaces with a dense material which appears ridge-like at high magnification. These ridges are oriented spirally along the cisternal surface of the tubule. They are regularly spaced at an interval of about 160 Å and have a pitch of about 45°. The functional significance of the cisternal coat is unknown. Sometimes, intracisternal tubules are observed to be contained within the lumina of the agranular cytoplasmic tubules. These intracisternal tubules are considered to be formed by an intracisternal deflection of only one leaflet of the unit membrane of the agranular cytoplasmic tubules. Membrane fusion is observed to occur between closely associated agranular cytoplasmic tubules.     

Male but not female mice with severe osteogenesis imperfecta are partially protected from high-fat diet-induced obesity

Previously we have shown that young mice with a dominant severe form of osteogenesis imperfecta (OI), caused by mutated collagen type I, exhibit an altered glucose/insulin metabolism and energy expenditure along with elevated levels of osteocalcin, a bone-derived hormone involved in the regulation of whole-body metabolism. This study aimed to examine the long-term effects of a western diet in these OI mice. Male and female OI mice and wild type littermates (WT) were fed a high-fat diet (HFD) or a matched low-fat diet (LFD) for 26 weeks. HFD-induced obesity was observed in male and female WT and female OI mice, but not in male OI mice. HFD-fed WT and OI mice of both sexes developed hyperglycemia and glucose intolerance, but the degree of glucose intolerance was significantly lower in male and female OI mice compared to sex- and diet-matched WT mice. Indirect calorimetry revealed increased movement of male OI mice on HFD compared to LFD and, while HFD lowered energy expenditure in WT mice, energy expenditure was not changed in OI mice. Further, HFD-fed male OI mice demonstrated a diet-induced increased expression of the thermogenesis genes, Ucp1 and Pgc1α, in brown adipose tissue. On LFD, total and Gla-13 osteocalcin levels were similar in 30-week-old WT and OI mice, but on HFD, both were significantly higher in OI mice than WT. Thus, male OI mice respond to HFD with increased movement, energy expenditure, brown adipose tissue thermogenesis, and higher levels of osteocalcin, resulting in partial protection against HFD-induced obesity.     

Natural history of blue sclerae in osteogenesis imperfecta

Scleral hue is an important sign which distinguishes 2 broad groupings of patients, those with and those without blue sclerae with non-lethal osteogenesis imperfecta (OI). Individuals with OI type I have distinctly blue sclerae which remain intensely blue throughout life. In OI type III and OI type IV the sclerae may also be blue at birth and during infancy, but the intensity fades with time such that these individuals have sclerae of normal hue by adolescence and adult life.     

The dentinal structure of equine incisors: a light and scanning electron-microscopic study

This paper gives an anatomical overview of the dentinal structure in equine incisor teeth with special reference to the three-dimensional organization, the number and the diameter of the dentinal tubules. The spatial arrangement of equine dentine was examined by scanning electron microscopy of occlusal surfaces and longitudinally fractured teeth and by light microscopy of both decalcified and ground sections. The dentinal tubules of the peripherally situated primary dentine were directly continuous with those of the circumpulpal secondary dentine. The tubules had numerous side branches along their entire course and ramified into terminal branches near the dentino-enamel junction. Tubules of tertiary dentine, situated in the centre of the dental star, were few in number and not continuous with those of the surrounding secondary dentine. On non-etched incisors tubular orifices were clogged by an amorphous smear layer that covered the occlusal surface. On etched occlusal surfaces the numerical tubular density was calculated in different zones. The largest number of tubules per unit area was situated in the secondary dentine forming the dark periphery of the dental star, whereas the smallest number was present in the tertiary dentine located in the pale centre of the dental star. Dentinal tubular diameters were measured at various distances from the pulp. They were widest near the pulpal wall and narrowed progressively towards the dentino-enamel junction. Tubular widths measured on etched occlusal surfaces were considerably larger than those measured on undecalcified incisors due to the removal of intratubular dentine during the etching process.     

Osteogenesis imperfecta type I with unusual dental abnormalities

A large kindred with dominantly inherited osteogenesis imperfecta was evaluated. Affected individuals had bone fractures, blue sclerae, and hearing loss. In addition, all had dental abnormalities distinct from those previously described in other families with this syndrome. Deciduous teeth were normal in color or blue-grey. On radiographs of an early developing deciduous dentition, pulps were larger than normal. In patients with mixed dentitions, pulp chambers of deciduous teeth were partially obliterated. Increased constriction at the junctions of the crowns and roots was found in some deciduous teeth. One patient had large pulp stones in the pulp chambers of all maxillary deciduous molars. Permanent teeth were normal in color but had oval pulp chambers with apical extensions into the coronal portions of the roots, large coronal pulp stones, narrow root canals, and thin roots. Individuals in this family who did not have osteogenesis imperfecta had normal teeth. In addition, a well circumscribed radiolucency without a sclerotic periphery, involving the apices of all permanent mandibular incisors, was found in the anterior mandible in one patient. These findings support the hypothesis that this family has yet another type I osteogenesis imperfecta "syndrome".     

Scalp-ear-nipple syndrome: Additional manifestations

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal dominant condition that causes aplasia cutis congenita of the scalp, alteration of the shape of the external ear, and hypoplasia of the nipple. Women in a new family, the fifth to be described, had virtually complete aplasia of the breast and a small skin dimple without any pigmentation instead of a normal nipple, although other affected women had normal breast and nipple development. Dental changes included widely spaced or missing secondary teeth; the ears were cupped or folded and stood out from the head, axillary apocrine secretion and axillary hair growth were reduced; and finger nails were brittle. There was no generalized abnormality of sweating. Some patients had partial syndactyly of the 3rd and 4th fingers, and complete cutaneous syndactyly of the 2nd and 3rd toes. © 1994 Wiley-Liss, Inc.     

常染色体隐性遗传性成骨不全症的分子遗传学研究进展

成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.     

常染色体隐性遗传性成骨不全症的分子遗传学研究进展

成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.     

常染色体隐性遗传性成骨不全症的分子遗传学研究进展

成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.     

Structure of the upper teeth of the filefish, Stephanolepis cirrhifer

The teeth of the filefish were investigated with light and scanning electron microscopy. Anterior and posterior rows of pleurodont teeth are present in the maxilla. The teeth in the anterior row possess a large labial and small lingual surface and the teeth in the posterior row possess a small labial and large lingual surface. The enameloid consists of three layers-the outer, middle, and inner layer. The outer layer consists of fine, parallel crystallites oriented perpendicular to the surface. They are similar to the crystallites in enamel derived from ectoderm. In the middle layer the crystallites form parallel bundles that are oriented in the same direction as that of the crystallites in the outer layer. In the inner layer bundles of crystallites interlace with each other. The tubular structures and the terminal branches of the dentinal tubules are located among the crystallites in the inner layer. In the dentine numerous dentinal tubules radiate from the pulp cavity toward the periphery and are seen to curve slightly in an S-shaped course. At the occlusal tip the alternating parabolic layers are seen and these are considered to be mineralized lines. The openings of the dentinal tubules are round or oval, surrounded by interlacing fibrils. The teeth are tightly fixed to the jawbone by bundles of fibrils. At the lower part of the lingual surface of the teeth in the anterior row and the labial surface of the teeth in the posterior row the bundles of fibrils start at the dentine and some fibrils run through connective tissue, while others terminate in projections of the jawbones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metanephric adenoma of the kidney: Ultrastructural, immunohistochemical and lectin histochemical studies

A case of metanephric adenoma, a rare benign tumor of the kidney is reported, and the results of ultrastructural, immunohistochemical, and lectin histochemical studies are presented. The patient was a 47 year old Japanese man presenting wlth a left renal tumor by ultrasonography. The nephrectomy material revealed a well-demarcated tumor with medullary appearance, and on histological examination the tumor was composed of cuboidal cells forming regular small tubules with hyallnous stroma. Incomplete glomeruloid structures were formed in a few elongated tubules com-posed of columnar cells. Metanephric blastema was not observed in the tumor or in the normal kidney. By electron microscope, the tumor cells were observed to be immature cells with microvilli at the apical surfaces. The neoplastic tubules were surrounded by basal lamina. The tumor cells were immunoreactive for Leu 7, epithelial membrane antigen, vimentin, and low molecular weight cytokeratin, and were weakly immunoreactive for S-100 protein. Peanut agglutinin, soybean agglutinin, and Dollchos bifiorus agglu-tinin were bound to the apical surfaces of the tumor cells.     

Enamel Structure and Composition in the Tricho-Dento-Osseous Syndrome

Tricho-dento-osseous syndrome (TDO) is an autosomal dominant disorder characterized by curly hair, hypoplastic enamel, taurodontism, and dense bone. The purpose of this investigation was to characterize the enamel defects in a TDO population in North Carolina. Twelve TDO teeth and 12 normal teeth were examined. The enamel thickness was decreased in all TDO teeth ranging from having no enamel to about 60% the thickness of normal teeth. Half of the TDO teeth had primarily prismless enamel while the remainder had at least occasional areas of prismatic enamel. TDO enamel crystallites appeared similar to normal crystallites with TEM. The mineral per volume of TDO enamel (n =9) (68.5%) was significantly less, on average, compared with normal enamel (n=8) (84.5). The genetic mutation responsible for the TDO phenotype results in alteration of a developmental pathway(s) common to hair, teeth and bone. This further illustrates that these embryologically diverse tissues share common developmental controls at the molecular level.     

Enamel structure and composition in the tricho-dento-osseous syndrome

Tricho-dento-osseous syndrome (TDO) is an autosomal dominant disorder characterized by curly hair, hypoplastic enamel, taurodontism, and dense bone. The purpose of this investigation was to characterize the enamel defects in a TDO population in North Carolina. Twelve TDO teeth and 12 normal teeth were examined. The enamel thickness was decreased in all TDO teeth ranging from having no enamel to about 60% the thickness of normal teeth. Half of the TDO teeth had primarily prismless enamel while the remainder had at least occasional areas of prismatic enamel. TDO enamel crystallites appeared similar to normal crystallites with TEM. The mineral per volume of TDO enamel (n = 9) (68.5%) was significantly less, on average, compared with normal enamel (n = 8) (84.5). The genetic mutation responsible for the TDO phenotype results in alteration of a developmental pathway(s) common to hair, teeth and bone. This further illustrates that these embryologically diverse tissues share common developmental controls at the molecular level.