Heterozygous variants are a frequent cause of amelogenesis imperfecta.

Background: Collagen XVII is most typically associated with human disease when biallelic variants (>230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous variants causing dominant non-syndromic AI is not widely recognised.

Methods: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for variants.

Review of 1.75 million referrals over 34 months identifies the disruptive impact of the SARS-CoV-2 pandemic on oral surgery care in England: a service evaluation.

Aims This study aimed to use electronic referral management system (eRMS) oral surgery data across multiple sites in England to evaluate the service over a 34-month period in relation to: 1) pre- and post-pandemic referral rates in oral surgery; 2) examining the data for signs of inequality in obtaining a referral for oral surgery; and 3) considering the impact on service provision for oral surgery in England.Methods Oral surgery referral data were available from an eRMS for areas of England covered by this service for the 34-month period of March 2019 to December 2021 (inclusive), which included 12 months of pre-pandemic data and the first 22 months of the pandemic. The data were from the following regions in England: Central Midlands; Cheshire and Merseyside; East Anglia and Essex; Greater Manchester; Lancashire; Thames Valley; and Yorkshire and the Humber.

The changing face of a dental school: a Leeds perspective.

Time spent as a student at a dental school leaves a legacy that shapes how each of us develops professionally and more generally as our lives progress. Personal reminiscences relate to our own time as a student. Comments years later that 'things are not the same' are true.

An evaluation of referrer factors for 98,671 referrals made to the West Yorkshire oral surgery managed clinical network over a three-year period.

Introduction Patients referred from primary dental care to hospital-based specialists in high volumes can contribute to significant NHS service pressures. Surprisingly, little is understood about what contributes to referral factors.Aims To gain new insight into the referral factors from primary dental care by interrogating the tri-speciality West Yorkshire managed clinical network (MCN) referral pathway data for a 36-month period (2016-2019).

Spectrum of pathogenic variants and founder effects in amelogenesis imperfecta associated with MMP20.

Amelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of 10 families with recessive hypomaturation AI revealed four novel and one known variants in the matrix metallopeptidase 20 (MMP20) gene that were predicted to be pathogenic. MMP20 encodes a protease that cleaves the developing extracellular enamel matrix and is necessary for normal enamel crystal growth during amelogenesis.

A missense mutation of Leu74Pro of OGR1 found in familial amelogenesis imperfecta actually causes the loss of the pH-sensing mechanism.

Ovarian cancer G protein-coupled receptor 1 (OGR1), also known as GPR68, is a proton-sensing G protein-coupled receptor (GPCR) coupling to G/phospholipase C/Ca signaling pathways. The specific histidine residues at the extracellular surface of OGR1 are suggested to be involved in the proton sensing. Later, some metal ions, including nickel ion (Ni), are also indicated to be OGR1 ligands.

A missense variant in specificity protein 6 (SP6) is associated with amelogenesis imperfecta.

Amelogenesis is the process of enamel formation. For amelogenesis to proceed, the cells of the inner enamel epithelium (IEE) must first proliferate and then differentiate into the enamel-producing ameloblasts. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective or absent tooth enamel.

New missense variants in RELT causing hypomineralised amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic diseases characterised by dental enamel malformation. Pathogenic variants in at least 33 genes cause syndromic or non-syndromic AI. Recently variants in RELT, encoding an orphan receptor in the tumour necrosis factor (TNF) superfamily, were found to cause recessive AI, as part of a syndrome encompassing small stature and severe childhood infections.

Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome.

Objectives: Variants in DLX3 cause tricho-dento-osseous syndrome (TDO, MIM #190320), a systemic condition with hair, nail and bony changes, taurodontism and amelogenesis imperfecta (AI), inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, six different DLX3 variants have been reported in TDO.

Dentin dysplasia: diagnostic challenges.

Dentin dysplasia(DD) is a rare autosomal dominant disorder associated with disturbance of the dentin. While the crowns appear clinically normal, on radiography, the pulp spaces appear partially or completely obliterated, with short blunted roots, and multiple periapical radiolucencies affecting the apparently sound teeth. Clinical signs include spontaneous abscess formation or increased tooth mobility which can lead to exfoliation.

Amelogenesis Imperfecta; Genes, Proteins, and Pathways.

Amelogenesis imperfecta (AI) is the name given to a heterogeneous group of conditions characterized by inherited developmental enamel defects. AI enamel is abnormally thin, soft, fragile, pitted and/or badly discolored, with poor function and aesthetics, causing patients problems such as early tooth loss, severe embarrassment, eating difficulties, and pain. It was first described separately from diseases of dentine nearly 80 years ago, but the underlying genetic and mechanistic basis of the condition is only now coming to light.

A Fourth Mutation Is Associated with Enamel Hypomineralisation and Structural Abnormalities.

"Amelogenesis imperfecta" (AI) describes a group of genetic conditions that result in defects in tooth enamel formation. Mutations in many genes are known to cause AI, including the gene encoding the serine protease, kallikrein related peptidase 4 (), expressed during the maturation stage of amelogenesis. In this study we report the fourth mutation to be identified in autosomal recessively-inherited hypomaturation type AI, c.

Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta.

We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.

Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.

'Amelogenesis imperfecta' (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans.

Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown.

Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI.

Spectrum of PEX1 and PEX6 variants in Heimler syndrome.

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction.

A distinctive oral phenotype points to FAM20A mutations not identified by Sanger sequencing.

Biallelic FAM20A mutations cause two conditions where Amelogenesis Imperfecta (AI) is the presenting feature: Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome; and Enamel Renal Syndrome. A distinctive oral phenotype is shared in both conditions. On Sanger sequencing of FAM20A in cases with that phenotype, we identified two probands with single, likely pathogenic heterozygous mutations.

Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6.

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. We ascertained eight families affected by HS and, by using a whole-exome sequencing approach, identified biallelic mutations in PEX1 or PEX6 in six of them. Loss-of-function mutations in both genes are known causes of a spectrum of autosomal-recessive peroxisome-biogenesis disorders (PBDs), including Zellweger syndrome.

Are plasma cell-rich inflammatory conditions of the oral mucosa manifestations of IgG4-related disease?

Aim: The aim of this study was to characterise plasma cell infiltrates, in terms of IgG4 positivity, in specific and non-specific plasma cell-rich chronic inflammatory conditions of the oral mucosa. Exploring the possibility that specific plasma cell-rich oral inflammatory conditions have association with or represent an oral manifestation of immunoglobulin G4-related disease (IgG4-RD).

Methods: Ten patients with plasma cell-rich chronic inflammatory conditions of the oral mucosa were identified (seven--plasma cell mucositis and three--non-specific diffuse oral mucosal inflammation with ulceration).

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations.

Background: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features.

Pathognomonic oral profile of Enamel Renal Syndrome (ERS) caused by recessive FAM20A mutations.

Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects. Commonly described as an isolated trait, it may be observed concomitantly with other orodental and/or systemic features such as nephrocalcinosis in Enamel Renal Syndrome (ERS, MIM#204690), or gingival hyperplasia in Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome (AIGFS, MIM#614253). Patients affected by ERS/AIGFS present a distinctive orodental phenotype consisting of generalized hypoplastic AI affecting both the primary and permanent dentition, delayed tooth eruption, pulp stones, hyperplastic dental follicles, and gingival hyperplasia with variable severity and calcified nodules.