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Molecular Genetics & Genomic Medicine May 2018Dentinogenesis imperfecta (DI) is a rare debilitating hereditary disorder affecting dentin formation and causing loss of the overlying enamel. Clinically, DI sufferers...
BACKGROUND
Dentinogenesis imperfecta (DI) is a rare debilitating hereditary disorder affecting dentin formation and causing loss of the overlying enamel. Clinically, DI sufferers have a discolored and weakened dentition with an increased risk of fracture. The aims of this study were to assess genotype-phenotype findings in three families with DI-II with special reference to mutations in the DSPP gene and clinical, histological, and imaging manifestations.
METHODS
Nine patients participated in the study (two from family A, four from family B, and three from family C). Buccal swab samples were collected from all participants and extracted for genomic DNA. Clinical and radiographic examinations had been performed longitudinally, and the dental status was documented using photographic images. Four extracted and decalcified tooth samples were prepared for histological analysis to assess dysplastic manifestations in the dentin. Optical coherence tomography (OCT) was applied to study the health of enamel tissue from in vivo images and the effect of the mutation on the function and structure of the DSPP gene was analyzed using bioinformatics software programs.
RESULTS
The direct DNA sequence analysis revealed three distinct mutations, one of which was a novel finding. The mutations caused dominant phenotypes presumably by interference with signal peptide processing and protein secretion. The clinical and radiographic disturbances in the permanent dentition indicated interfamilial variability in DI-II manifestations, however, no significant intrafamilial variability was observed.
CONCLUSION
The different mutations in the DSPP gene were accompanied by distinct phenotypes. Enamel defects suggested deficit in preameloblast function during the early stages of amelogenesis.
Topics: Adolescent; Adult; Child; Child, Preschool; Dental Enamel; Dentin; Dentinogenesis Imperfecta; Family; Female; Genotype; Humans; Male; Middle Aged; Mutation; Netherlands; Pedigree; Phenotype; Sequence Analysis, DNA; Tooth
PubMed: 29512331
DOI: 10.1002/mgg3.375 -
A homozygous mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies.JBMR Plus May 2024Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects...
Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by and , respectively. The main extra-skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, :c. 946C > T is a rare homozygous variant causing OI with extra-skeletal features in inbred Arab populations.
PubMed: 38562913
DOI: 10.1093/jbmrpl/ziae026 -
The Saudi Dental Journal Oct 2013Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia....
Dentinogenesis imperfecta (DI) associated with osteogenesis imperfecta (OI) is a genetic disorder that affects the connective tissues and results in dentine dysplasia. This case report discusses the systemic and dental manifestations of OI and DI in a 4-year-old child, with moderate presentation of both disorders, who was treated at King Fahd Military Medical Complex in Dhahran. Dental treatment included the use of strip and stainless-steel crowns under local anesthesia, as well as behavior modification techniques. Rigorous home care instructions, including reinforcement of the oral hygiene practice and avoidance of any episode that may lead to bone fracture, were discussed with the parents. The case was reevaluated at 3-month follow-up visits, wherein the medical and dental histories were updated, the child's growth was monitored, periodic clinical and radiographic examinations were performed, and the oral hygiene was evaluated via the debris index score and caries risk assessment. Further treatment of the permanent dentition may be needed in the future.
PubMed: 24371383
DOI: 10.1016/j.sdentj.2013.10.004 -
European Journal of Medical Genetics Nov 2023Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and...
Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management.
Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia. We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures. None of them had rickets, blue sclera or dentinogenesis imperfecta. ALP serum levels were low and genetics revealed in the four probands heterozygous pathogenic mutations in COL1A2 c.838G > A (p.Gly280Ser) and in ALPL c.1333T > C (p.Ser445Pro). After multidisciplinary meeting, a diagnostic transiliac bone biopsy was indicated for each sibling for therapeutic decision. Bone histology and histomorphometry, as compared to reference values of children with OI type I as well as, to a control pediatric patient harboring the same COL1A2 mutation, revealed similarly decreased trabecular bone volume, increased osteocyte lacunae, but additionally severe osteomalacia. Quantitative backscattered electron imaging demonstrated that bone matrix mineralization was not as decreased as expected for osteomalacia. In summary, we observed within each biopsy samples classical features of OI and classical features of HPP. The apparent nearly normal bone mineralization density distribution results presumably from divergent effects of OI and HPP on matrix mineralization. A combination therapy was initiated with ALP enzyme-replacement and one month later with bisphosphonates. The ongoing treatment led to improved skeletal growth, increased BMD and markedly reduced fracture incidence.
Topics: Child; Humans; Osteogenesis Imperfecta; Hypophosphatasia; Osteomalacia; Fractures, Multiple; Mutation; Alkaline Phosphatase; Calcinosis; Rickets
PubMed: 37758163
DOI: 10.1016/j.ejmg.2023.104856 -
Indian Journal of Dental Research :... 2019Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate.... (Review)
Review
Dentinogenesis Imperfecta and dentin dysplasia are genetic oral diseases inherited in a simple autosomal dominant mode, with high penetrance and a low mutation rate. Both of them are present with bulbous crowns, marked cervical constrictions, severe attritions, few periapical radiolucencies, and premature tooth loss. The diagnosis is based on family history, and detailed clinical examination, while genetic diagnosis may become useful in the future once sufficient disease-causing mutations have been discovered. Here, we present a case with overlapping features of both dentinogenesis imperfecta and dentin dysplasia asserting both the anomalies to be part of the same continuum of the genetic event.
Topics: Dentin; Dentin Dysplasia; Dentinogenesis Imperfecta; Extracellular Matrix Proteins; Humans; Pedigree; Phosphoproteins; Sialoglycoproteins
PubMed: 31745067
DOI: 10.4103/ijdr.IJDR_318_18 -
Indian Journal of Dental Research :... 2010In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late,... (Review)
Review
In oral cavity, the spectrum of diseases due to genetic alterations ranges from developmental disturbances of teeth to the pre-cancerous and cancerous lesions. Of late, significant progress has been made in the molecular analysis of tumors. With molecular genetic testing emerging as diagnostic, prognostic, and therapeutic approach, a review of genetic alterations ranging from the development of oro-facial structures to the tumors in the head and neck region are addressed in this article. The functional regulatory aspect of genes in relation to oro-facial structures are discussed separately, i.e., in relation to tooth genesis, tooth agenesis (non-syndromic, syndromic), tooth structural alterations, syndromic oro-facial defects, bone diseases, skin diseases (genodermatoses), and malignant tumors. In this literature, various genes involved in the development of the oro-facial structures and tooth in particular are discussed. The genetic basis of disorders in the tooth development (agenesis, hypodontia), tooth structural defects like amelogenesis imperfecta (AI), dentinogenesis imperfecta (DI), and oro-facial structural alterations (various syndromes) are explained.
Topics: Anodontia; Craniofacial Abnormalities; Ectodermal Dysplasia; Genes, Homeobox; Humans; Odontogenesis; Tooth Abnormalities
PubMed: 20657100
DOI: 10.4103/0970-9290.66646 -
Genes May 2022Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II...
Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.
Topics: Animals; Dentinogenesis Imperfecta; Extracellular Matrix Proteins; Humans; Mice; Mutation; Pedigree; Phosphoproteins; Sialoglycoproteins
PubMed: 35627243
DOI: 10.3390/genes13050858 -
Journal of Personalized Medicine Jun 2021Hereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral...
Hereditary dentin defects can be categorized as a syndromic form predominantly related to osteogenesis imperfecta (OI) or isolated forms without other non-oral phenotypes. Mutations in the gene encoding dentin sialophosphoprotein (DSPP) have been identified to cause dentinogenesis imperfecta (DGI) Types II and III and dentin dysplasia (DD) Type II. While DGI Type I is an OI-related syndromic phenotype caused mostly by monoallelic mutations in the genes encoding collagen type I alpha 1 chain () and collagen type I alpha 2 chain (). In this study, we recruited families with non-syndromic dentin defects and performed candidate gene sequencing for exons and exon/intron boundaries. Three unrelated Korean families were further analyzed by whole-exome sequencing due to the lack of the mutation, and heterozygous mutations were identified: c.3233G>A, p.(Gly1078Asp) in Family 1 and c.1171G>A, p.(Gly391Ser) in Family 2 and 3. Haplotype analysis revealed different disease alleles in Families 2 and 3, suggesting a mutational hotspot. We suggest expanding the molecular genetic etiology to include for isolated dentin defects in addition to .
PubMed: 34201399
DOI: 10.3390/jpm11060526 -
International Journal of Nanomedicine 2019Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the...
INTRODUCTION
Dentinogenesis imperfecta type 1 (OIDI) is considered a relatively rare genetic disorder (1:5000 to 1:45,000) associated with osteogenesis imperfecta. OIDI impacts the formation of collagen fibrils in dentin, leading to morphological and structural changes that affect the strength and appearance of teeth. However, there is still a lack of understanding regarding the nanoscale characterization of the disease, in terms of collagen ultrastructure and mechanical properties. Therefore, this research presents a qualitative and quantitative report into the phenotype and characterization of OIDI in dentin, by using a combination of imaging, nanomechanical approaches.
METHODS
For this study, 8 primary molars from OIDI patients and 8 primary control molars were collected, embedded in acrylic resin and cut into longitudinal sections. Sections were then demineralized in 37% phosphoric acid using a protocol developed in-house. Initial experiments demonstrated the effectiveness of the demineralization protocol, as the ATR-FTIR spectral fingerprints showed an increase in the amide bands together with a decrease in phosphate content. Structural and mechanical analyses were performed directly on both the mineralized and demineralized samples using a combination of scanning electron microscopy, atomic force microscopy, and Wallace indentation.
RESULTS
Mesoscale imaging showed alterations in dentinal tubule morphology in OIDI patients, with a reduced number of tubules and a decreased tubule diameter compared to healthy controls. Nanoscale collagen ultrastructure presented a similar D-banding periodicity between OIDI and controls. Reduced collagen fibrils diameter was also recorded for the OIDI group. The hardness of the (mineralized) control dentin was found to be significantly higher (p<0.05) than that of the OIDI (mineralized) dentine. Both the exposed peri- and intratubular dentinal collagen presented bimodal elastic behaviors (Young's moduli). The control samples presented a stiffening of the intratubular collagen when compared to the peritubular collagen. In case of the OIDI, this stiffening in the collagen between peri- and intratubular dentinal collagen was not observed and the exposed collagen presented overall a lower elasticity than the control samples.
CONCLUSION
This study presents a systematic approach to the characterization of collagen structure and properties in OIDI as diagnosed in dentin. Structural markers for OIDI at the mesoscale and nanoscale were found and correlated with an observed lack of increased elastic moduli of the collagen fibrils in the intratubular OIDI dentin. These findings offer an explanation of how structural changes in the dentin could be responsible for the failure of some adhesive restorative materials as observed in patients affected by OIDI.
Topics: Collagen; Dentin; Dentinogenesis Imperfecta; Elasticity; Hardness; Humans; Molar; Osteogenesis Imperfecta; Phenotype; Radiography, Bitewing; Spectroscopy, Fourier Transform Infrared; Tooth Demineralization
PubMed: 31819441
DOI: 10.2147/IJN.S217420 -
Journal - Oklahoma Dental Association 2007
Topics: Adult; Chromosomes, Human, Pair 4; Dentinogenesis Imperfecta; Humans; Male; Tooth Discoloration
PubMed: 17802895
DOI: No ID Found