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Zhonghua Kou Qiang Yi Xue Za Zhi =... Aug 2023Tooth replacement disorders are characterized by retention of deciduous teeth and abnormalities in permanent teeth eruption. Hereditary disorders with multiple teeth...
Tooth replacement disorders are characterized by retention of deciduous teeth and abnormalities in permanent teeth eruption. Hereditary disorders with multiple teeth involved include cleidocranial dysplasia, osteopetrosis and Gardner syndrome. These rare diseases have great difficulty in treatment with various principles reported. This article focused on clinical manifestations and early treatment principles of these hereditary disorders, as well as the important role of dentists in early diagnosis of these diseases.
PubMed: 37550037
DOI: 10.3760/cma.j.cn112144-20230403-00131 -
Genes Jul 2023Mutations in the mouse microphthalmia-associated transcription factor () gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to...
Mutations in the mouse microphthalmia-associated transcription factor () gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to hypopigmentation, microphthalmia, deafness, and blindness. For instance, an association has been established between loss-of-function mutations in the mouse gene and a variety of human retinal diseases, including Waardenburg type 2 and Tietz syndromes. Although there is evidence showing that mice with the homozygous mutation manifest microphthalmia and osteopetrosis, there are limited or no data on the effects of the heterozygous condition in the eye. mice can therefore be regarded as an important model system for the study of human disease. Thus, we characterized mice at 1, 3, 12, and 18 months old in comparison with age-matched wild-type mice. The light- and dark-adapted electroretinogram (ERG) recordings showed progressive cone-rod dystrophy in mice. The RPE response was reduced in the mutant in all age groups studied. Progressive loss of pigmentation was found in mice. Histological retinal sections revealed evidence of retinal degeneration in mice at older ages. For the first time, we report a mouse model of progressive cone-rod dystrophy and RPE dysfunction with a mutation in the gene.
Topics: Animals; Mice; Cone-Rod Dystrophies; Microphthalmia-Associated Transcription Factor; Microphthalmos; Retinal Dystrophies; Retinal Pigment Epithelium
PubMed: 37510362
DOI: 10.3390/genes14071458 -
Bone Oct 2023
Topics: Humans; Osteopetrosis; Osteosclerosis
PubMed: 37482207
DOI: 10.1016/j.bone.2023.116854 -
Clinical Genetics Sep 2023Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process.... (Meta-Analysis)
Meta-Analysis Review
Tooth eruption is an important and unique biological process during craniofacial development. Both the genetic and environmental factors can interfere with this process. Here we aimed to find the failure pattern of tooth eruption among five genetic diseases. Both systematic review and meta-analysis were used to identify the genotype-phenotype associations of unerupted teeth. The meta-analysis was based on the characteristics of abnormal tooth eruption in 223 patients with the mutations in PTH1R, RUNX2, COL1A1/2, CLCN7, and FAM20A respectively. We found all the patients presented selective failure of tooth eruption (SFTE). Primary failure of eruption patients with PTH1R mutations showed primary or isolated SFTE1 in the first and second molars (59.3% and 52% respectively). RUNX2 related cleidocranial dysplasia usually had SFTE2 in canines and premolars, while COL1A1/2 related osteogenesis imperfecta mostly caused SFTE3 in the maxillary second molars (22.9%). In CLCN7 related osteopetrosis, the second molars and mandibular first molars were the most affected. While FAM20A related enamel renal syndrome most caused SFTE5 in the second molars (86.2%) and maxillary canines. In conclusion, the SFTE was the common characteristics of most genetic diseases with abnormal isolated or syndromic tooth eruption. The selective pattern of unerupted teeth was gene-dependent. Here we recommend SFTE to classify those genetic unerupted teeth and guide for precise molecular diagnosis and treatment.
Topics: Humans; Tooth Eruption; Tooth, Unerupted; Core Binding Factor Alpha 1 Subunit; Tooth Abnormalities; Phenotype; Genotype; Chloride Channels
PubMed: 37448157
DOI: 10.1111/cge.14400 -
Current Osteoporosis Reports Oct 2023Recently, there has been an increasing number of studies on the crosstalk between the bone and the bone marrow and how it pertains to anemia. Here, we discuss four... (Review)
Review
PURPOSE OF REVIEW
Recently, there has been an increasing number of studies on the crosstalk between the bone and the bone marrow and how it pertains to anemia. Here, we discuss four heritable clinical syndromes contrasting those in which anemia affects bone growth and development, with those in which abnormal bone development results in anemia, highlighting the multifaceted interactions between skeletal development and hematopoiesis.
RECENT FINDINGS
Anemia results from both inherited and acquired disorders caused by either impaired production or premature destruction of red blood cells or blood loss. The downstream effects on bone development and growth in patients with anemia often constitute an important part of their clinical condition. We will discuss the interdependence of abnormal bone development and growth and hematopoietic abnormalities, with a focus on the erythroid lineage. To illustrate those points, we selected four heritable anemias that arise from either defective hematopoiesis impacting the skeletal system (the hemoglobinopathies β-thalassemia and sickle cell disease) versus defective osteogenesis resulting in impaired hematopoiesis (osteopetrosis). Finally, we will discuss recent findings in Diamond Blackfan anemia, an intrinsic disorder of both the erythron and the bone. By focusing on four representative hereditary hematopoietic disorders, this complex relationship between bone and blood should lead to new areas of research in the field.
Topics: Humans; Bone Marrow; Anemia; Hematopoiesis; Bone and Bones
PubMed: 37436584
DOI: 10.1007/s11914-023-00809-3 -
Journal of Clinical and Translational... Aug 2023We report a patient with refractory ascites because of portal hypertension caused by hemochromatosis secondary to osteopetrosis. To our knowledge, this is the first...
We report a patient with refractory ascites because of portal hypertension caused by hemochromatosis secondary to osteopetrosis. To our knowledge, this is the first well-documented case of this association. A 46-year-old male patient who was repeatedly infused with red blood cells for anemia secondary to osteopetrosis suffered from refractory ascites. The serum-ascites albumin gradient was 29.9 g/L. Abdominal computed tomography (CT) showed a large amount of ascites, hepatomegaly, and splenomegaly. Bone marrow biopsy showed a small bone marrow cavity with no hematopoietic tissue. A peripheral blood smear showed tear drop red blood cells and metarubricytes. Serum ferritin was 8,855.0 ng/mL. Therefore, we considered that the ascites resulted from portal hypertension caused by hemochromatosis secondary to osteopetrosis. We simultaneously performed the transjungular intrahepatic portal-systemic shunt (TIPS) and obtained a transjungular liver biopsy. The portal pressure gradient before TIPS was 28 mmHg, and iron staining was strongly positive on liver biopsy, which confirmed our diagnosis. After TIPS, both abdominal distention and ascites gradually resolved, and no recurrence as observed after the 12-month postoperative follow-up was observed. This case indicated that regular monitoring of iron load is important for patients with osteopetrosis. TIPS is safe and effective for portal hypertension complications due to osteopetrosis.
PubMed: 37408812
DOI: 10.14218/JCTH.2022.00418 -
Clinical Genetics Sep 2023The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus.... (Review)
Review
The GNAS locus is an imprinted site. The α-subunit of the stimulatory G protein (Gsα) and extralarge variant (XLαs) are the two important products of the GNAS locus. The abnormal expression of Gsα is associated with pseudohypoparathyroidism (PHP) and related disorders, including Albright hereditary osteodystrophy (AHO), pseudopseudohypoparathyroidism (PPHP), and progressive osseous heteroplasia (POH). XLαs protein can mimic the catalytic intracellular synthesis of cyclic adenosine monophosphate (cAMP) by Gsα in response to parathyroid hormone (PTH) stimulation, which may be involved in the pathogenesis of PPHP and POH in patients with paternal GNAS defects. A paternally inherited nonsense variant in the first exon of XLαs in an adult patient may be associated with fractures and osteopetrosis. The relationship between the XLαs product of the GNAS locus and bone remodeling may have been overlooked. Here, we summarize the phenotypes of genetic mouse models and clinical cases of XLαs variations and suggest that the abnormal paternal expression of XLαs may be associated with the development of POH and affect osteoblast and osteoclast differentiation.
Topics: Humans; Animals; Mice; Bone Density; Chromogranins; GTP-Binding Protein alpha Subunits, Gs; Pseudohypoparathyroidism; Mutation
PubMed: 37249323
DOI: 10.1111/cge.14378 -
Journal of Veterinary Dentistry Dec 2023Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella),...
Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella), the persistence of deciduous teeth, and impaction of permanent teeth. Jaw swelling due to osteomyelitis is often the reason that cats with PADS are presented for veterinary dental care. The clinical history, oral examination findings, dental radiological findings, and histopathology were evaluated for 13 cats with dental and skeletal pathology consistent with PADS, including 9 with osteomyelitis. Cats in this study were predominantly domestic shorthair (12 of 13 cats), and there was no apparent sex predilection. All cats had multiple persistent deciduous teeth and multiple impacted permanent teeth, although the number of persistent and impacted teeth varied. Osteomyelitis of the jaw typically occurred within the first 4 years of life. Osteomyelitis of the mandible was 4 times more common than osteomyelitis of the maxilla. Histologically, osteomyelitis was chronic, neutrophilic, and osteoproliferative. Necrotic bone was confirmed in 67% of osteomyelitis lesions. Histological evaluation of jaws without inflammation demonstrated abnormal amounts of unmodeled bone, abnormally dense bone, and retention of cartilage in the caudal mandible. Three cats in the study had mandibular distoclusion and 2 had concurrent paronychia. To obtain a favorable clinical outcome in PADS cats with jaw swelling, prompt and aggressive surgical treatment of osteomyelitis is required. Extraction of persistent deciduous teeth and impacted permanent teeth is recommended when there is associated periodontitis or osteomyelitis.
Topics: Cats; Animals; Pathology, Oral; Fractures, Bone; Tooth, Impacted; Maxilla; Osteomyelitis; Cat Diseases
PubMed: 37248965
DOI: 10.1177/08987564231175594 -
Bone Aug 2023Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth....
Osteopetrosis (OPT) denotes the consequences from failure of osteoclasts to resorb bone and chondroclasts to remove calcified physeal cartilage throughout growth. Resulting impairment of skeletal modeling, remodeling, and growth compromises widening of medullary spaces, formation of the skull, and expansion of cranial foramina. Thus, myelophthisic anemia, raised intracranial pressure, and cranial nerve palsies complicate OPT when severe. Osteopetrotic bones fracture due to misshaping, failure of remodeling to weave the collagenous matrix of cortical osteons and trabeculae, persistence of mineralized growth plate cartilage, "hardening" of hydroxyapatite crystals, and delayed healing of skeletal microcracks. Teeth may fail to erupt. Now it is widely appreciated that OPT is caused by germline loss-of-function mutation(s) usually of genes involved in osteoclast function, but especially rarely of genes necessary for osteoclast formation. Additionally, however, in 2003 we published a case report demonstrating that prolonged excessive dosing during childhood of the antiresorptive aminobisphosphonate pamidronate can sufficiently block osteoclast and chondroclast activity to recapitulate the skeletal features of OPT. Herein, we include further evidence of drug-induced OPT by illustrating osteopetrotic skeletal changes from repeated administration of high doses of the aminobisphosphonate zoledronic acid (zoledronate) given to children with osteogenesis imperfecta.
Topics: Child; Humans; Osteopetrosis; Osteoclasts; Zoledronic Acid; Fractures, Bone; Skull
PubMed: 37172883
DOI: 10.1016/j.bone.2023.116788 -
Journal of Pediatric Endocrinology &... Jul 2023Osteopetrorickets is a rare complication of autosomal recessive ("malignant") osteopetrosis. Its prompt diagnosis is essential, because early suspicion of infantile...
Osteopetrorickets is a rare complication of autosomal recessive ("malignant") osteopetrosis. Its prompt diagnosis is essential, because early suspicion of infantile osteopetrosis enables treatment with human stem cell transplantation, depending on the gene involved. It is important to identify not only the characteristic radiological changes of rickets, but also the coexistence of increased bone density, so as not to miss this very rare entity. Herein, a brief case report is presented.
Topics: Humans; Osteopetrosis; Rickets; Hypophosphatemia; Radiography; Hematopoietic Stem Cell Transplantation
PubMed: 37141118
DOI: 10.1515/jpem-2023-0001