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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 -
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 -
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 -
Revista Cientifica Odontologica... 2023The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this...
The main origin of amelogenesis imperfecta (AI) is a genetic alteration inherited by a family member which affects the dental enamel of the teeth of a person with this condition in various ways. The present clinical case from the Teaching Dental Clinic of the Peruvian University Cayetano Heredia is of a 6-year 5-month-old male child who came to the dental office accompanied by his father and 8-year-old sister, diagnosed with the same AI condition. The comprehensive treatment proposed for this patient was determined by radiographic and clinical examinations and consultations with specialists in different areas. The purpose of this publication was to report a case and describe possible clinical approaches.
PubMed: 38288452
DOI: 10.21142/2523-2754-1102-2023-156 -
Frontiers in Physiology 2023Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar-incisor...
Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar-incisor hypomineralization (MIH), a prevalent disease in children originating from environmental and epigenetic factors. MIH enamel presents as the abnormal enamel marked by loss of translucency, demarcation between the healthy and affected enamel, and reduced mineral content. The pathophysiology of opaque, demarcated enamel lesions is not understood; however, the retention of enamel proteins in the matrix has been suggested. Ameloblastin (Ambn) is an enamel protein of the secreted calcium-binding phosphoproteins (SCPPs) critical for enamel formation. When the gene is mutated or deleted, teeth are affected by hypoplastic amelogenesis imperfecta. In this study, enamel formation in mice was analyzed when transgenic was overexpressed from the amelogenin promoter encoding full-length Ambn. was under- and overexpressed at six increasing concentrations in separate mouse lines. Mice overexpressing displayed opaque enamel at low concentrations and demarcated lesions at high concentrations. The severity of enamel lesions increased starting from the inner enamel close to the dentino-enamel junction (DEJ) to span the entire width of the enamel layer in demarcated areas. Associated with the opaque enamel were 17-kDa Ambn cleavage products, a prolonged secretory stage, and a thin basement membrane in the maturation stage. Ambn accumulations found in the innermost enamel close to the DEJ and the mineralization front correlated with reduced mineral content. Demarcated enamel lesions were associated with Ambn species of 17 kDa and higher, prolonged secretory and transition stages, a thin basement membrane, and shortened maturation stages. Hypomineralized opacities were delineated against the surrounding mineralized enamel and adjacent to ameloblasts detached from the enamel surface. Inefficient Ambn cleavage, loss of contact between ameloblasts, and the altered basement membrane curtailed the endocytic activity; thus, enamel proteins remained unresorbed in the matrix. Ameloblasts have the ability to distinguish between Ambn concentration and Ambn cleavage products through finely tuned feedback mechanisms. The under- or overexpression of Ambn in murine secretory ameloblasts results in either hypoplastic amelogenesis imperfecta or hypomineralization with opaque or sharply demarcated boundaries of lesions, similar to MIH.
PubMed: 38274050
DOI: 10.3389/fphys.2023.1233391 -
Iranian Journal of Biotechnology Oct 2023Dental enamel formation is a complex process that is regulated by various genes. One such gene, Family With Sequence Similarity 83 Member H (Fam83h), has been identified...
BACKGROUND
Dental enamel formation is a complex process that is regulated by various genes. One such gene, Family With Sequence Similarity 83 Member H (Fam83h), has been identified as an essential factor for dental enamel formation. Additionally, Fam83h has been found to be potentially linked to the Wnt/β-catenin pathway.
OBJECTIVES
This study aimed to investigate the effects of the Fam83h knockout gene on mineralization and formation of teeth, along with mediators of the Wnt/β-catenin pathway as a development aspect in mice.
MATERIALS AND METHODS
To confirm the Fam83h-KnockOut mice, both Sanger sequencing and Western blot methods were used. then used qPCR to measure the expression levels of genes related to tooth mineralization and formation of dental root, including Fam20a, Dspp, Dmp1, Enam, Ambn, Sppl2a, Mmp20, and Wnt/β-catenin pathway mediators, in both the Fam83h-Knockout and wild-type mice at 5, 11 and 18 days of age. also the expression level of Fgf10 and mediators of the Wnt/β-catenin pathway was measured in the skin of both Knockout and wild-type mice using qPCR. A histological assessment was then performed to further investigate the results.
RESULTS
A significant reduction in the expression levels of Ambn, Mmp20, Dspp, and Fgf10 in the dental root of Fam83h-Knockout mice compared to their wild-type counterparts was demonstrated by our results, indicating potential disruptions in tooth development. Significant down-regulation of CK1a, CK1e, and β-catenin in the dental root of Fam83h-Knockout mice was associated with a reduction in mineralization and formation-related gene. Additionally, the skin analysis of Fam83h-Knockout mice revealed reduced levels of Fgf10, CK1a, CK1e, and β-catenin. Further histological assessment confirmed that the concurrent reduction of Fgf10 expression level and Wnt/β-catenin genes were associated with alterations in hair follicle maturation.
CONCLUSIONS
The concurrent reduction in the expression level of both Wnt/β-catenin mediators and mineralization-related genes, resulting in the disruption of dental mineralization and formation, was caused by the deficiency of Fam83h. Our findings suggest a cumulative effect and multi-factorial interplay between Fam83h, Wnt/Β-Catenin signaling, and dental mineralization-related genes subsequently, during the dental formation process.
PubMed: 38269199
DOI: 10.30498/ijb.2023.391902.3673 -
Heliyon Jan 2024Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without...
Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (:c.132delG; p.Pro45Argfs*25) and (:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of . We are reporting variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of .
PubMed: 38192829
DOI: 10.1016/j.heliyon.2023.e23688 -
Heliyon Jan 2024Amelogenesis imperfecta is a rare genetic disorder that interferes with normal enamel formation. Of the 4 main types of amelogenesis imperfecta, hypoplastic (type 1) is...
Amelogenesis imperfecta is a rare genetic disorder that interferes with normal enamel formation. Of the 4 main types of amelogenesis imperfecta, hypoplastic (type 1) is the most prevalent, characterized by a quantitative alteration in enamel. The pitting or reduced thickness of the enamel results in generalized hypersensitivity, increased susceptibility to caries and infection, attrition, and a loss in vertical dimension of occlusion. Prosthodontic management of these patients can be challenging not only functionally and restoratively, but also from an emotional and psychosocial standpoint. This clinical report describes the prosthodontic management and rehabilitation of two young adult siblings with hypoplastic (type 1) amelogenesis imperfecta.
PubMed: 38192821
DOI: 10.1016/j.heliyon.2023.e23939