Publikace se zaměřuje na různé vzácné nemoci v orofaciální oblasti, především v zubním lékařství. Určeno odborné veřejnosti.; Z pohledu medicíny jsou vzácná onemocnění charakterizována velkým počtem a širokou rozmanitostí poruch a příznaků, které se mohou lišit i v rámci jednoho syndromu, ne pouze navzájem mezi jednotlivými nemocemi. Stejné onemocnění pak může mít více podtypů a u postižených osob mohou být odlišné klinické projevy. Vliv na délku života se u jednotlivých vzácných onemocnění značně liší, některé tyto nemoci způsobují úmrtí již při narození, mnohé jsou degenerativní nebo ohrožující život, zatímco jiné jsou s normálním životem slučitelné, pokud jsou včas diagnostikovány a správně léčeny. Předkládaná monografie se věnuje problematice vzácných onemocnění a jejich projevů v orofaciální oblasti, především z pohledu zubního lékaře. Úvodní kapitola se kromě základních definic zabývá klasifikačními systémy, které jsou u jednotlivých onemocnění uváděny společně s názvem, synonymy, prevalencí a typem dědičnosti. Největší část knihy obsahuje více než padesát kazuistik, jež podávají konkrétní obrazy onemocnění a jsou doplněny bohatou obrazovou dokumentací. Poruchy vývoje zubů se pro svoji relativně snadnou diagnostiku jeví jako vhodný marker vývojových vad orofaciální krajiny, a monografie proto bude vhodným doplněním poznatků i pro další lékařské obory.

• MeSH
• Mouth Diseases MeSH
• Face pathology   MeSH
• Pathology, Oral MeSH
• Oral Medicine MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• vzácné nemoci
• zubní lékařství
• NML Publication type
• kolektivní monografie

• MeSH
• Stomatognathic System Abnormalities diagnosis   therapy   MeSH
• Amelogenesis Imperfecta * diagnosis   therapy   MeSH
• Humans MeSH
• Rare Diseases diagnosis   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

OBJECTIVES: Dental caries is a widespread multifactorial disease, caused by the demineralization of hard dental tissues. Susceptibility to dental caries is partially genetically conditioned; this study was aimed at finding an association of selected single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in amelogenesis with this disease in children. MATERIALS AND METHODS: In this case-control study, 15 SNPs in ALOX15, AMBN, AMELX, KLK4, TFIP11, and TUFT1 genes were analyzed in 150 children with primary dentition and 611 children with permanent teeth with/without dental caries from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) cohort. RESULTS: Dental caries in primary dentition was associated with SNPs in AMELX (rs17878486) and KLK4 (rs198968, rs2242670), and dental caries in permanent dentition with SNPs in AMELX (rs17878486) and KLK4 (rs2235091, rs2242670, rs2978642), (p ≤ 0.05). No significant differences between cases and controls were observed in the allele or genotype frequencies of any of the selected SNPs in ALOX15, AMBN, TFIP11, and TUFT1 genes (p > 0.05). Some KLK4 haplotypes were associated with dental caries in permanent dentition (p ≤ 0.05). CONCLUSIONS: Based on this study, we found that although the SNPs in AMELX and KLK4 are localized in intronic regions and their functional significance has not yet been determined, they are associated with susceptibility to dental caries in children. CLINICAL RELEVANCE: AMELX and KLK4 variants could be considered in the risk assessment of dental caries, especially in permanent dentition, in the European Caucasian population.

• MeSH
• Amelogenesis * genetics   MeSH
• Amelogenin genetics   MeSH
• Child MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Case-Control Studies MeSH
• Dental Caries * genetics   epidemiology   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH

Ameloblasts are specialized epithelial cells in the jaw that have an indispensable role in tooth enamel formation-amelogenesis1. Amelogenesis depends on multiple ameloblast-derived proteins that function as a scaffold for hydroxyapatite crystals. The loss of function of ameloblast-derived proteins results in a group of rare congenital disorders called amelogenesis imperfecta2. Defects in enamel formation are also found in patients with autoimmune polyglandular syndrome type-1 (APS-1), caused by AIRE deficiency3,4, and in patients diagnosed with coeliac disease5-7. However, the underlying mechanisms remain unclear. Here we show that the vast majority of patients with APS-1 and coeliac disease develop autoantibodies (mostly of the IgA isotype) against ameloblast-specific proteins, the expression of which is induced by AIRE in the thymus. This in turn results in a breakdown of central tolerance, and subsequent generation of corresponding autoantibodies that interfere with enamel formation. However, in coeliac disease, the generation of such autoantibodies seems to be driven by a breakdown of peripheral tolerance to intestinal antigens that are also expressed in enamel tissue. Both conditions are examples of a previously unidentified type of IgA-dependent autoimmune disorder that we collectively name autoimmune amelogenesis imperfecta.

• MeSH
• Ameloblasts metabolism   MeSH
• Amelogenesis Imperfecta * complications   immunology   MeSH
• Antigens immunology   metabolism   MeSH
• Polyendocrinopathies, Autoimmune * complications   immunology   MeSH
• Autoantibodies * immunology   MeSH
• Celiac Disease * complications   immunology   MeSH
• Immunoglobulin A immunology   MeSH
• Humans MeSH
• AIRE Protein deficiency   MeSH
• Proteins immunology   metabolism   MeSH
• Intestines immunology   metabolism   MeSH
• Dental Enamel immunology   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop's classification (Witkop, J Oral Pathol, 1988, 17, 547-553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative. Objectives: We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management. Methods: Individuals presenting with so called "isolated" or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/). Results: GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with MMP20 and FAM83H for isolated AI. FAM20A and LTBP3 genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie ACP4 or digenic inheritance. Conclusion: NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI (CNNM4, WDR72, FAM20A ... ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop's AI classification.

• Publication type
• Journal Article MeSH

• MeSH
• Amelogenesis Imperfecta * rehabilitation   MeSH
• Esthetics, Dental MeSH
• Humans MeSH
• Adolescent MeSH
• Zirconium MeSH
• Dental Veneers MeSH
• Denture, Partial, Fixed MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Úvod a cíl: Amelogenesis imperfecta sdružuje klinicky a geneticky heterogenní skupinu vývojových vad ovlivňujících vzhled a strukturu skloviny, jež více či méně těžce postihují všechny funkce chrupu. Projevy amelogenesis imperfecta jsou ze strany pacientů vnímány jako kompromitace estetiky a zvýšená citlivost zubů. Důsledky onemocnění dopadají neblaze na dospívající jedince, kteří se začleňují do kolektivů a hledají své místo ve společnosti. Tradiční postup léčby může být velmi nákladný a může vyžadovat jistou míru psychické odolnosti pacienta z důvodu bolestivosti a časové náročnosti ošetření. Tyto požadavky léčby spolu s nedostatečnou tloušťkou vrstvy sekundárního dentinu tak často nutí lékaře odložit ošetření, což může nepříznivě ovlivnit psychosociální vývoj pacienta. Vlastní pozorování: Patnáctiletá pacientka byla odeslána na protetické oddělení pro kompletní rekonstrukci stálého chrupu s diagnózou hypoplastické amelogenesis imperfecta. Vzhledem k charakteru onemocnění byla vykonána bezodkladná přímá rekonstrukce. Závěr: Bezpreparační přístup je možný i ve věku dospívání. Jsou zachovány tvrdé zubní tkáně, není ohrožena vitalita zubní dřeně a je snížena psychická zátěž pacienta. K přímé rekonstrukci je tak možno přistoupit za předpokladu spolupráce pacienta. Tento přístup musí být spojen s důslednou úpravou povrchu zubu za účelem omezení adheze a retence plaku. Výhodou také je, že případné dílčí selhání rekonstrukce je u přímé rekonstrukce poměrně jednoduše opravitelné.

Introduction and aim: Amelogenesis imperfecta associates a clinically and genetically heterogeneous group of developmental defects affecting the appearance and structure of enamel, which more or less severely affect all dental functions. Manifestations of amelogenesis imperfecta are considered by patients to be a compromise of aesthetics and increased tooth sensitivity. The consequences of the disease have a detrimental effect on adolescents who integrate into groups and seek their place in society. However, the traditional treatment approach can be very expensive and may require a certain degree of psychological resilience of the patient due to the pain and time consuming treatment. These treatment requirements, together with the insufficient thickness of the secondary dentin layer, thus often force the physician to delay treatment, which may adversely affect the patient's psychosocial development. Self-observation: A fifteen-year-old patient was sent to the prosthetic department for complete reconstruction of permanent teeth with a diagnosis of hypoplastic amelogenesis imperfecta. Due to the nature of the disease, immediate direct reconstruction was performed. Conclusion: An unprepared approach is possible even in adolescence. Hard dental tissues are preserved, the vitality of the dental pulp is not endangered and the patient's psychological burden is reduced. Direct reconstruction can be approached provided the patient cooperates. This approach must be combined with consistent treatment of the tooth surface to reduce adhesion and plaque retention. The advantage is also that any partial failure of the reconstruction is relatively easy to repair in the case of direct reconstruction.

• Keywords
• přímá rekonstrukce,
• MeSH
• Amelogenesis Imperfecta * therapy   MeSH
• Esthetics, Dental MeSH
• Humans MeSH
• Adolescent MeSH
• Congenital Abnormalities MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Učební texty pro studenty zubního lékařství, které se zaměřují na mikroskopickou anatomii.

• MeSH
• Anatomy MeSH
• Microscopy MeSH
• Dentistry MeSH

• Conspectus
• Anatomie člověka a srovnávací anatomie
• NML Fields
• anatomie
• zubní lékařství
• NML Publication type
• učebnice vysokých škol

Genomics methodologies have significantly improved elucidation of Mendelian disorders. The combination with high-throughput functional-omics technologies potentiates the identification and confirmation of causative genetic variants, especially in singleton families of recessive inheritance. In a cohort of 99 individuals with abnormal Golgi glycosylation, 47 of which being unsolved, glycomics profiling was performed of total plasma glycoproteins. Combination with whole-exome sequencing in 31 cases revealed a known genetic defect in 15 individuals. To identify additional genetic factors, hierarchical clustering of the plasma glycomics data was done, which indicated a subgroup of four patients that shared a unique glycomics signature of hybrid type N-glycans. In two siblings, compound heterozygous mutations were found in SLC10A7, a gene of unknown function in human. These included a missense mutation that disrupted transmembrane domain 4 and a mutation in a splice acceptor site resulting in skipping of exon 9. The two other individuals showed a complete loss of SLC10A7 mRNA. The patients' phenotype consisted of amelogenesis imperfecta, skeletal dysplasia, and decreased bone mineral density compatible with osteoporosis. The patients' phenotype was mirrored in SLC10A7 deficient zebrafish. Furthermore, alizarin red staining of calcium deposits in zebrafish morphants showed a strong reduction in bone mineralization. Cell biology studies in fibroblasts of affected individuals showed intracellular mislocalization of glycoproteins and a defect in post-Golgi transport of glycoproteins to the cell membrane. In contrast to yeast, human SLC10A7 localized to the Golgi. Our combined data indicate an important role for SLC10A7 in bone mineralization and transport of glycoproteins to the extracellular matrix.

• MeSH
• Zebrafish genetics   growth & development   metabolism   MeSH
• Adult MeSH
• Exome MeSH
• Phenotype MeSH
• Fibroblasts metabolism   pathology   MeSH
• Calcification, Physiologic * MeSH
• Genomics * MeSH
• Glycomics * MeSH
• Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase deficiency   MeSH
• Glycosylation MeSH
• Golgi Apparatus metabolism   pathology   MeSH
• Cohort Studies MeSH
• Infant MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Young Adult MeSH
• Mutation * MeSH
• Organic Anion Transporters, Sodium-Dependent genetics   metabolism   MeSH
• Pedigree MeSH
• Symporters genetics   metabolism   MeSH
• Protein Transport MeSH
• Congenital Disorders of Glycosylation complications   MeSH
• Bone Diseases, Developmental etiology   metabolism   pathology   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH