Genetic Variants in the Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis.

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, and , have been linked to Ramon syndrome.

Rare Filaggrin Variants Are Associated with Pustular Skin Diseases in Asians.

Reactive pustular eruptions (RPEs) can manifest in a variety of conditions, including pustular psoriasis (PP) and adult-onset immunodeficiency syndrome due to anti-interferon-γ autoantibody (AOID). These RPEs can be attributed to different causes, one of which is genetic factors. However, the genetic basis for pustular skin diseases remains poorly understood.

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role.

LRP4 mutations, dental anomalies, and oral exostoses.

Background: In order to generate a normal set of teeth, fine-tuning of Wnt/β-catenin signaling is required, in which WNT ligands bind to their inhibitors or WNT inhibitors bind to their co-receptors. Lrp4 regulates the number of teeth and their morphology by modulating Wnt/β-catenin signaling as a Wnt/β-catenin activator or inhibitor, depending on its interactions with the partner proteins, such as Sostdc1 and Dkk1.

Aim: To investigate genetic etiologies of dental anomalies involving LRP4 in a Thai cohort of 250 children and adults with dental anomalies.

Heterozygous Variants in Are Associated with Mesiodens, Supernumerary Teeth, Oral Exostoses, and Odontomas.

Background: Supernumerary teeth refer to extra teeth that exceed the usual number of dentitions. A mesiodens is a particular form of supernumerary tooth, which is located in the premaxilla region. The objective of the study was to investigate the genetic etiology of extra tooth phenotypes, including mesiodens and isolated supernumerary teeth.

Genetic Variants in Protein Tyrosine Phosphatase Non-Receptor Type 23 Are Responsible for Mesiodens Formation.

A mesiodens is a supernumerary tooth located in the midline of the premaxilla. To investigate the genetic cause of mesiodens, clinical and radiographic examination were performed on 23 family members of a two-generation Hmong family. Whole exome sequencing (WES) or Sanger sequencing were performed in 22 family members and two unrelated Thai patients with mesiodens.

Rare Genetic Variants in Human Are Implicated in Mesiodens and Isolated Supernumerary Teeth.

The activation of Wnt/β-catenin signalling is a prerequisite for odontogenesis. APC, a member of the AXIN-CK1-GSK3β-APC β-catenin destruction complex, functions to modulate Wnt/β-catenin signalling to establish regular teeth number and positions. APC loss-of-function mutations are associated with the over-activation of WNT/β-catenin signalling and subsequent familial adenomatous polyposis (FAP; MIM 175100) with or without multiple supernumerary teeth.

A Mutation in Is Associated with Multiple Supernumerary Cusps and Root Maldevelopment.

Background: Enamel knots and Hertwig epithelial root sheath (HERS) regulate the growth and folding of the dental epithelium, which subsequently determines the final form of tooth crown and roots. We would like to investigate the genetic etiology of seven patients affected with unique clinical manifestations, including multiple supernumerary cusps, single prominent premolars, and single-rooted molars.

Methods: Oral and radiographic examination and whole-exome or Sanger sequencing were performed in seven patients.

A Founder Intronic Variant in Likely Results in Aberrant Splicing and Protein Truncation in Patients of Karen Descent with Osteogenesis Imperfecta Type VIII.

One of the most important steps in post-translational modifications of collagen type I chains is the hydroxylation of carbon-3 of proline residues by prolyl-3-hydroxylase-1 (P3H1). Genetic variants in have been reported to cause autosomal recessive osteogenesis imperfecta (OI) type VIII. Clinical and radiographic examinations, whole-exome sequencing (WES), and bioinformatic analysis were performed in 11 Thai children of Karen descent affected by multiple bone fractures.

, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis.

Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare and severe pustular autoinflammatory skin disease in which acute generalized erythema and scaling develop with numerous sterile pustules. GPP shares skin manifestations, especially pustular skin reaction, with adult-onset immunodeficiency (AOID) with anti-interferon-γ autoantibodies, an autoimmune disease.

Methods: Clinical examinations and whole-exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction.

Loss of Function Variant as a Contributing Factor in Generalized Pustular Psoriasis and Adult-Onset Immunodeficiency.

Background: Generalized pustular psoriasis (GPP; MIM 614204) is a rare multisystemic autoinflammatory disease, characterized by episodes of acute generalized erythema and scaling developed with the spread of numerous sterile pustules. Adult-onset immunodeficiency syndrome (AOID) with anti-interferon-γ autoantibodies is an immunodeficiency disorder associated with disruptive IFN-γ signaling.

Methods: Clinical examination and whole exome sequencing (WES) were performed on 32 patients with pustular psoriasis phenotypes and 21 patients with AOID with pustular skin reaction.

Dental Anomalies in Ciliopathies: Lessons from Patients with , and Mutations.

Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis−van Creveld syndrome and two patients with Bardet−Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis−van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes.

Subtotal Parathyroidectomy Successfully Controls Calcium Levels of Patients with Neonatal Severe Hyperparathyroidism Carrying a Novel CASR Mutation.

Introduction: Inactivating mutations of the calcium-sensing receptor (CASR) gene result in neonatal severe hyperparathyroidism (NSHPT). Total parathyroidectomy is an effective way to control life-threatening hypercalcemia in NSHPT but leads to permanent hypoparathyroidism. An alternative surgical option is subtotal parathyroidectomy.

Clinical and Genetic Studies of the First Monozygotic Twins with Pfeiffer Syndrome.

Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.

Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.

Objective: The objective of this study was to investigate molecular etiologies of oral exostoses and dental anomalies in 14 patients from eight families.

Methods: Oral and radiographic examinations were performed on every patient. Whole exome and Sanger sequencing were performed on DNA of the patients, the unaffected parents and unaffected siblings.

Novel Dental Anomaly-associated Mutations in WNT10A Protein Binding Sites.

Objective: WNT/β-catenin signaling is initiated by binding of a WNT protein to a Frizzled (FZD) receptor and a co-receptor, low-density lipoprotein (LDL) receptor-related protein 5 or 6 (LRP5/6). The objective of this study was to find the genetic variants responsible for dental anomalies found in 4 families.

Methods: Clinical and radiographic examination and whole exome sequencing were performed on 5 patients affected with dental anomalies and the mutant proteins modeled.

Expanding genotypic and phenotypic spectrums of LTBP3 variants in dental anomalies and short stature syndrome.

Mutations in LTBP3 are associated with Dental Anomalies and Short Stature syndrome (DASS; MIM 601216), which is characterized by hypoplastic type amelogenesis imperfecta, hypodontia, underdeveloped maxilla, short stature, brachyolmia, aneurysm and dissection of the thoracic aorta. Here we report a novel (p.Arg545ProfsTer22) and a recurrent (c.

Distal renal tubular acidosis, autoimmune thyroiditis, enamel hypomaturation, and tooth agenesis caused by homozygosity of a novel double-nucleotide substitution in SLC4A4.

Background: Mutations in SLC4A4 have been reported to be associated with proximal renal tubular acidosis (RTA), short stature, band keratopathy, cataract, glaucoma, and hypoplastic-type amelogenesis imperfecta. In this study, the authors describe the clinical manifestations, and investigate the molecular etiology, in a patient with RTA.

Case Description: The authors report on a girl with distal RTA who carried a novel homozygous base substitution of 2 consecutive base pair variants (NM_001098484.

Cryptophthalmos, dental anomalies, oral vestibule defect, and a novel FREM2 mutation.

FREM2 is a member of the FREM2-FRAS1-FREM1 protein complex which contributes to epithelial-mesenchymal coupling. We report a Thai woman with cryptophthalmos, dental anomalies, and oral vestibule defect. A compound heterozygous mutation (c.

SERPINA1, generalized pustular psoriasis, and adult-onset immunodeficiency.

Adult-onset immunodeficiency syndrome (AOID) with anti-interferon (IFN)-γ autoantibodies is characterized by an AIDS-like illness with disruptive IFN-γ signaling. Patients generally present with recurrent and disseminated opportunistic infections along with neutrophilic dermatoses. Generalized pustular psoriasis (GPP; Online Mendelian Inheritance in Man #614204) is characterized by acute generalized erythema and scaling with numerous aseptic pustules.

A novel P3H1 mutation is associated with osteogenesis imperfecta type VIII and dental anomalies.

Objective: Our objective was to investigate the molecular etiology of osteogenesis imperfecta type VIII and dental anomalies in 4 siblings of a Karen tribe family.

Materials And Methods: Four patients and their unaffected parents were studied by clinical and radiographic examination. In situ hybridization of P3h1 during early murine tooth development, whole-exome sequencing, and Sanger direct sequencing were performed.

Juberg-Hayward syndrome and Roberts syndrome are allelic, caused by mutations in ESCO2.

Objective: Juberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, hypoplasia or aplasia of thumbs, short stature, dislocation of radial head, and fusion of humerus and radius leading to elbow restriction. A homozygous mutation in ESCO2 has recently been reported to cause Juberg-Hayward syndrome. Our objective was to investigate the molecular etiology of Juberg-Hayward syndrome in two affected Lisu tribe brothers.

Harboyan syndrome: novel SLC4A11 mutation, clinical manifestations, and outcome of corneal transplantation.

Harboyan syndrome or corneal dystrophy and progressive deafness (MIM #217400) is characterized by congenital hereditary endothelial dystrophy (CHED) and progressive, sensorineural hearing loss. Mutations in SLC4A11 are responsible for this rare genetic syndrome. Eight patients from seven unrelated families affected with Harboyan Syndrome with mean follow-up of 12.