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Clinical Case Reports Mar 2024Treatment of patients with amelogenesis imperfecta extends over many years, from childhood to early adulthood. Their management at any age is complex and has to be...
Treatment of patients with amelogenesis imperfecta extends over many years, from childhood to early adulthood. Their management at any age is complex and has to be adapted in relation to therapies validated in the general population.
PubMed: 38523819
DOI: 10.1002/ccr3.8704 -
JAMA Dermatology May 2024Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe...
IMPORTANCE
Kindler epidermolysis bullosa is a genetic skin-blistering disease associated with recessive inherited pathogenic variants in FERMT1, which encodes kindlin-1. Severe orofacial manifestations of Kindler epidermolysis bullosa, including early oral squamous cell carcinoma, have been reported.
OBJECTIVE
To determine whether hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa.
DESIGN, SETTINGS, AND PARTICIPANTS
This longitudinal, 2-center cohort study was performed from 2003 to 2023 at the Epidermolysis Bullosa Centre, University of Freiburg, Germany, and the Special Care Dentistry Clinic, University of Chile in association with DEBRA Chile. Participants included a convenience sampling of all patients with a diagnosis of Kindler epidermolysis bullosa.
MAIN OUTCOMES AND MEASURES
The primary outcomes were the presence of hypoplastic pitted amelogenesis imperfecta, intraoral wounds, gingivitis and periodontal disease, gingival hyperplasia, vestibular obliteration, cheilitis, angular cheilitis, chronic lip wounds, microstomia, and oral squamous cell carcinoma.
RESULTS
The cohort consisted of 36 patients (15 female [42%] and 21 male [58%]; mean age at first examination, 23 years [range, 2 weeks to 70 years]) with Kindler epidermolysis bullosa. The follow-up ranged from 1 to 24 years. The enamel structure was assessed in 11 patients, all of whom presented with enamel structure abnormalities. The severity of hypoplastic pitted amelogenesis imperfecta varied from generalized to localized pitting. Additional orofacial features observed include gingivitis and periodontal disease, which was present in 90% (27 of 30 patients) of those assessed, followed by intraoral lesions (16 of 22 patients [73%]), angular cheilitis (24 of 33 patients [73%]), cheilitis (22 of 34 patients [65%]), gingival overgrowth (17 of 26 patients [65%]), microstomia (14 of 25 patients [56%]), and vestibular obliteration (8 of 16 patients [50%]). Other features included chronic lip ulcers (2 patients) and oral squamous cell carcinoma with lethal outcome (2 patients).
CONCLUSIONS AND RELEVANCE
These findings suggest that hypoplastic pitted amelogenesis imperfecta is a feature of Kindler epidermolysis bullosa and underscore the extent and severity of oral manifestations in Kindler epidermolysis bullosa and the need for early and sustained dental care.
Topics: Humans; Male; Female; Adult; Young Adult; Child, Preschool; Adolescent; Child; Epidermolysis Bullosa; Middle Aged; Longitudinal Studies; Periodontal Diseases; Carcinoma, Squamous Cell; Amelogenesis Imperfecta; Cohort Studies; Mouth Neoplasms; Gingivitis; Cheilitis; Chile
PubMed: 38506824
DOI: 10.1001/jamadermatol.2024.0065 -
International Endodontic Journal Jun 2024Loss-of-function mutations in FAM20A result in amelogenesis imperfecta IG (AI1G) or enamel-renal syndrome, characterized by hypoplastic enamel, ectopic calcification,...
AIM
Loss-of-function mutations in FAM20A result in amelogenesis imperfecta IG (AI1G) or enamel-renal syndrome, characterized by hypoplastic enamel, ectopic calcification, and gingival hyperplasia, with some cases reporting spontaneous tooth infection. Despite previous reports on the consequence of FAM20A reduction in gingival fibroblasts and transcriptome analyses of AI1G pulp tissues, suggesting its involvement in mineralization and infection, its role in deciduous dental pulp cells (DDP) remains unreported. The aim of this study was to evaluate the properties of DDP obtained from an AI1G patient, providing additional insights into the effects of FAM20A on the mineralization of DDP.
METHODOLOGY
DDP were obtained from a FAM20A-AI1G patient (mutant cells) and three healthy individuals. Cellular behaviours were examined using flow cytometry, MTT, attachment and spreading, colony formation, and wound healing assays. Osteogenic induction was applied to DDP, followed by alizarin red S staining to assess their osteogenic differentiation. The expression of FAM20A-related genes, osteogenic genes, and inflammatory genes was analysed using real-time PCR, Western blot, and/or immunolocalization. Additionally, STRING analysis was performed to predict potential protein-protein interaction networks.
RESULTS
The mutant cells exhibited a significant reduction in FAM20A mRNA and protein levels, as well as proliferation, migration, attachment, and colony formation. However, normal FAM20A subcellular localization was maintained. Additionally, osteogenic/odontogenic genes, OSX, OPN, RUNX2, BSP, and DSPP, were downregulated, along with upregulated ALP. STRING analysis suggested a potential correlation between FAM20A and these osteogenic genes. After osteogenic induction, the mutant cells demonstrated reduced mineral deposition and dysregulated expression of osteogenic genes. Remarkably, FAM20A, FAM20C, RUNX2, OPN, and OSX were significantly upregulated in the mutant cells, whilst ALP, and OCN was downregulated. Furthermore, the mutant cells exhibited a significant increase in inflammatory gene expression, that is, IL-1β and TGF-β1, whereas IL-6 and NFκB1 expression was significantly reduced.
CONCLUSION
The reduction of FAM20A in mutant DDP is associated with various cellular deficiencies, including delayed proliferation, attachment, spreading, and migration as well as altered osteogenic and inflammatory responses. These findings provide novel insights into the biology of FAM20A in dental pulp cells and shed light on the molecular mechanisms underlying AI1G pathology.
Topics: Humans; Amelogenesis Imperfecta; Cell Differentiation; Cells, Cultured; Dental Enamel Proteins; Dental Pulp; Gene Expression; Mutation; Nephrocalcinosis; Osteogenesis; Tooth, Deciduous
PubMed: 38477421
DOI: 10.1111/iej.14056 -
Cureus Feb 2024This clinical case report details the comprehensive diagnosis and dental management of a seven-year-old female patient diagnosed with the rare genetic disorder,...
This clinical case report details the comprehensive diagnosis and dental management of a seven-year-old female patient diagnosed with the rare genetic disorder, amelogenesis imperfecta and gingival fibromatosis syndrome (AIGFS). The case initially presented as congenital adrenal hyperplasia and amelogenesis imperfecta, but further genetic analysis revealed the involvement of AIGFS due to a mutation in the gene. Diagnosis, confirmed through whole exome sequencing, clinical assessment, and laboratory tests, necessitated a multidisciplinary approach to address the treatment of such cases. The article underscores the critical importance of diagnosing and managing dental manifestations in pediatric patients with complex genetic conditions, highlighting the difficulties of treating AIGFS in mixed dentition. This case also highlights the indispensable role of pediatric dentists in diagnosing and treating these cases, ultimately improving the quality of life for individuals with AIGFS.
PubMed: 38465125
DOI: 10.7759/cureus.53787 -
Journal of Medical Genetics Jun 2024Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical...
BACKGROUND
Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic and variants have so far been associated with Mendelian genetic disease.
METHODS
Eight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice.
RESULTS
Rare biallelic pathogenic variants in plexin B2 (), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. expression was detected in differentiating ameloblasts.
CONCLUSION
We identify rare biallelic pathogenic variants in as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in knockout mice, and, together with the rarity of human variants, may explain why pathogenic variants in have not been reported previously.
Topics: Humans; Animals; Male; Female; Mice; Intellectual Disability; Pedigree; Amelogenesis Imperfecta; Receptors, Cell Surface; Nerve Tissue Proteins; Alleles; Child; Hearing Loss; Hearing Loss, Sensorineural; Adult; Mutation; Adolescent; Child, Preschool; Phenotype
PubMed: 38458752
DOI: 10.1136/jmg-2023-109728 -
The International Journal of... Feb 2024The purpose of the study was to examine the long-term performance of bonded all-ceramic restorations, veneers in particular, in patients with Amelogenesis Imperfecta...
PURPOSE
The purpose of the study was to examine the long-term performance of bonded all-ceramic restorations, veneers in particular, in patients with Amelogenesis Imperfecta (AI). There are few studies of long-term outcome using a minimally invasive procedure in these patients. This aspect is essential when treating young patients. All-ceramic restorations, especially veneers, offer a more tissue-preserving treatment but rely on a successful bonding. Due to the defect enamel in AI patients, the bond strength is however lower.
MATERIAL AND METHODS
A retro-prospective evaluation of 40 subjects with AI (26 women, 14 men) was provided with a total of 360 bonded restorations (282 veneers, 78 crowns). The restorations were evaluated according to complications, survival- and success rate.
RESULTS
The patients were observed up to 25,3 years (mean 15,4 ± 4,3 years). The mean age when receiving the restorations was 18,5 (± 4,2) years. There had been 59 (16,4%) restorations with prosthetic complications of which 29 (8.1%) had been remade (6 due to esthetic reasons, all in one patient) and 30 (8.3%) recemented (60% caused by trauma). We found 11 teeth with caries and 3 with endodontic complications. The over-all survival rate was 91,9% and the over-all success rate was 83,6%.
CONCLUSION
Bonded all-ceramic restorations with no active retention in AI patients perform excellent. The most common complications were debonding and fractures. The treatment should be on individual indications and been preceded by a multidisciplinary approach.
PubMed: 38408131
DOI: 10.11607/ijp.8493 -
Journal of Dental Research Apr 2024
Topics: Humans; Ameloblasts; Dental Enamel; Amelogenesis Imperfecta; Autophagy
PubMed: 38380491
DOI: 10.1177/00220345241231770 -
FASEB Journal : Official Publication of... Feb 2024This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were...
This study investigated the possible roles of renal estrogen receptors (ER) in glomerulonephritis associated with small vessel vasculitis. The relationships of ERs were investigated in antineutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis and immunoglobulin A (IgA) nephropathy groups, which are small vessel vasculitis subtypes with two different glomerulonephritis development pathophysiologies. The design of this study was prepared as a retrospective cohort study. The study included 42 patients with ANCA-associated vasculitis and 18 with IgA nephropathy in the small vessel vasculitis group. For the control group, intact renal tissues of 28 patients who underwent nephrectomy due to renal cell carcinoma were used. Renal biopsy samples of the groups were stained with ER beta (ß) and ER alpha (α). Tubular ER ß expression score (TERßES) median values were found to be significantly higher in ANCA- associated vasculitis (B = 0.724, OR [95%CI]: 2.064 [1.141-3.731], p = .016) and IgA nephropathy (B = 0.898, OR [95%CI]: 2.454 [1.307-4.609], p = .005) than in intact kidney tissue. It was determined that tubular ERß was most frequently localized in the distal tubule at 57.9% and the second most common in the proximal tubule at 20.4%. The expression of tubular ERß is increased in glomerulonephritis due to small vessel vasculitis. Tubular ERßs are most commonly localized in the distal tubule. Further studies are needed to understand the physiological and pathophysiological effects of altered renal ER levels in small vessel vasculitis.
Topics: Humans; Receptors, Estrogen; Glomerulonephritis, IGA; Antibodies, Antineutrophil Cytoplasmic; Retrospective Studies; Kidney; Glomerulonephritis; Vasculitis; Kidney Neoplasms; Estrogens; Amelogenesis Imperfecta; Nephrocalcinosis
PubMed: 38376916
DOI: 10.1096/fj.202302362RR -
European Archives of Paediatric... Feb 2024Amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are two groups of genetically inherited conditions resulting in abnormal enamel and dentin formation,...
BACKGROUND
Amelogenesis imperfecta (AI) and dentinogenesis imperfecta (DI) are two groups of genetically inherited conditions resulting in abnormal enamel and dentin formation, respectively. Children and young people may be adversely affected by these conditions, with significant reduction in oral health related quality of life. Dental management of children with AI and DI is often complex, which is exacerbated by the absence of clear referral pathways and scarce evidence-based guidelines.
METHOD
The need for increased knowledge and peer support led to the development of a group of UK paediatric dentists with a special clinical interest in the management of children with AI and DI.
PURPOSE
The aims of this paper are to describe the establishment of an AI/DI Clinical Excellence Network (AI/DI CEN) in paediatric dentistry including outputs and future plans, and to share our collective learning to help support others anywhere in the world advance the care of people with AI or DI.
Topics: Child; Humans; Adolescent; Amelogenesis Imperfecta; Dentinogenesis Imperfecta; Quality of Life; Dentin; United Kingdom
PubMed: 38308725
DOI: 10.1007/s40368-023-00859-2 -
Journal of Dental Sciences Jan 2024Amelogenesis imperfecta (AI), an assemblage of genetic diseases with dental enamel malformations, is generally grouped into hypoplastic, hypomaturation, and...
BACKGROUND/PURPOSE
Amelogenesis imperfecta (AI), an assemblage of genetic diseases with dental enamel malformations, is generally grouped into hypoplastic, hypomaturation, and hypocalcified types. This study aimed to identify the genetic etiology for a consanguineous Iranian family with autosomal recessive hypocalcified AI.
MATERIALS AND METHODS
Dental defects were characterized, and whole exome analysis conducted to search for disease-causing mutations. Minigene assay and RT-PCR were performed to evaluate molecular consequences of the identified mutation and expression of the causative gene in human dental tissues.
RESULTS
The defective enamel of erupted teeth showed extensive post-eruptive failure and discoloration. Partial enamel hypoplasia and indistinct dentino-enamel junction were evident on unerupted teeth, resembling hypocalcified AI. A novel homozygous (previously designated ) mutation of single-nucleotide deletion (NG_032974.1:g.5103del, NM_178497.5:c.67+1del) was identified to be disease-causing. The mutation would cause a frameshift to different transcript variant (TV) products: p.(Ala23Hisfs∗29) for TV1 and p.(Gly23Aspfs∗140) for TV2. Both dental pulps of developing and exfoliating primary teeth expressed TV2.
CONCLUSION
Loss-of-function mutations can cause AI type IIIB (the hypocalcified, autosomal recessive type), rather than type IIA4 (the hypomaturation, pigmented autosomal recessive type). This study supports a hypothesis that the product of TV2 is the single dominant ODAPH protein isoform critical for dental enamel formation and may also play an unappreciated role in development and homeostasis of dentin-pulp complex. Due to genetic heterogeneity and a nonideal genotype-phenotype correlation of AI, it is essential to perform genetic testing for patients with inherited enamel defects to make a definitive diagnosis.
PubMed: 38303846
DOI: 10.1016/j.jds.2023.09.020