Roles of the histone methyltransferase SET domain bifurcated 1 in epithelial cells during tooth development.

OBJECTIVE: This study aimed to reveal the effects of SET domain bifurcated 1 (SETDB1) on epithelial cells during tooth development. DESIGN: We generated conditional knockout mice (Setdb1fl/fl,Keratin14-Cre+ mice), in which Setdb1 was deleted only in epithelial cells. At embryonic day 14.5 (E14.5), immunofluorescence staining was performed to confirm the absence of SETDB1 within the epithelium of tooth embryos from Setdb1fl/fl,Keratin14-Cre+ mice. Mouse embryos were harvested after reaching embryonic day 13.5 (E13.5), and sections were prepared for histological analysis. To observe tooth morphology in detail, electron microscopy and micro-CT analysis were performed at postnatal months 1 (P1M) and 6 (P6M). Tooth embryos were harvested from postnatal day 7 (P7) mice, and the epithelial components of the tooth embryos were isolated and examined using quantitative RT-PCR for the expression of genes involved in tooth development. RESULTS: Setdb1fl/fl,Keratin14-Cre+ mice exhibited enamel hypoplasia, brittle and fragile dentition, and significant abrasion. Coronal sections displayed abnormal ameloblast development, including immature polarization, and a thin enamel layer that detached from the dentinoenamel junction at P7. Electron microscopic analysis revealed characteristic findings such as an uneven surface and the absence of an enamel prism. The expression of Msx2, Amelogenin (Amelx), Ameloblastin (Ambn), and Enamelin (Enam) was significantly downregulated in the epithelial components of tooth germs in Setdb1fl/fl,Keratin14-Cre+ mice. CONCLUSIONS: These results indicate that SETDB1 in epithelial cells is important for tooth development and clarify the relationship between the epigenetic regulation of SETDB1 and amelogenesis imperfecta for the first time.

[Research progress in regional odontodysplasia].

Regional odontodysplasia (ROD) is a rare localized dental developmental anomaly. The typical clinical manifestations of ROD are abnormal tooth eruption, abnormal development of enamel and dentin. The radiographic characteristic is "ghost teeth". Its etiology still remains unknown. The care and treatment of a patient with ROD needs a multidisciplinary approach. And the treatment should be taken after the assessment of each individual case of ROD. This paper reviews the definition, etiology, epidemiological features, clinical manifestations, imaging features, dental microstructure and treatment strategies of ROD to provide reference for clinical diagnosis and treatment.

Japanese 17q12 Deletion Syndrome with Complex Clinical Manifestations.

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis - A cross sectional study.

OBJECTIVES: Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. METHODS: A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. RESULTS: 64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. CONCLUSION: In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. CLINICAL SIGNIFICANCE: Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

Chapter 4: Development Defects of Enamel and Dentine and Coronal Caries.

The development of the human dentition is prone to disruption due to its delicate and complex nature - including variations in tooth number and anatomical form and in the characteristics of enamel, dentine, and cementum. This chapter will focus on developmental defects of dental enamel (DDE) and dentine (DDD), which can be associated with considerable treatment burden on an individual, often related to the change in dental hard tissue characteristics in those at increased caries risk. DDE are prevalent and can be related to genetic conditions such as amelogenesis imperfecta and environmental challenges such as direct physical trauma to the developing tooth or systemic insults during the different phases of amelogenesis. Phenotypical variability can be great, making diagnosis difficult in many cases. There are two major enamel defects - the quantitative defect of hypoplasia and the qualitative defect of hypomineralization. DDDs are less prevalent than DDEs, with two major DDD types: dentinogenesis imperfecta and dentine dysplasia. The main features of the DDDs are enamel fracture exposing the dentine and subsequent wear, with enlarged pulp spaces in some variants. The appearance may be affected, with bulbous teeth and grey-blue to brown opalescent colouring. With respect to dental caries, developmental defects of the teeth, in themselves, do not cause caries risk; however, they can change the manifestation of the disease due to creating niches for biofilm accumulation and thereby increasing cleaning difficulty and changing the physical and chemical characteristics of dental hard tissues and how they react to cariogenic challenges.

Prevalence and influence of dental development anomalies in smile esthetics: a cross-sectional analysis

Aim: To determine the prevalence of dental development anomalies and type of influence on the smile of adolescent students. Method: This was a cross-sectional and analytical study carried out in two public (A1) and two private (A2) schools chosen by lot in the city of Parnaíba-Piauí. The sample calculation was based on the target population: number of people enrolled in public and private schools between 15 and 19 years, in the city of Parnaíba-PI, which totaled 6209 students in 2020, according to a survey carried out by the Brazilian Institute of Geography and Statistics ­ IBGE. A questionnaire on epidemiological data and aesthetic self-perception of the smile was applied to 160 adolescents between 15 and 19 years old, from August 2020 to July 2021. The clinical examination was carried out under natural light, to check for the presence of anomaly(s) in the dental development. Students who presented only one pathology would be called group 1 (G1), those who presented two would be called group 2 (G2) and those who presented 3 or more would be called group 3 (G3). On the other hand, adolescents in whom no anomaly was evidenced would participate in the control group (CG), both in A1 and A2. Results: It was observed that 37.5% of the sample had only a type of dental anomaly, corresponding to 60 individuals. The most prevalent were enamel hypoplasia, fusion, transposition, agenesis, ectopic eruption, microdent and dens-in-dent. It was possible to verify a higher prevalence in the maxilla, private schools (76.6%) and females (86.6%). In 45% of adolescents with dental anomalies, embarrassment was observed when smiling. Conclusion: The prevalence was relatively high, highlighting the enamel hypoplasia, influencing the smile esthetics of a reasonable number of adolescents, whether for acquaintances, strangers or even for photographs

A case of familial recurrent 17q12 microdeletion syndrome presenting with severe diabetic ketoacidosis.

BACKGROUND: Heterozygous intragenic mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B) located on chromosome 17 and microdeletion of 17q12 region (17q12MD) leads to the complete loss of this gene, which causes renal cystic disease, diabetes mellitus (MODY5), hypomagnesemia, hyperuricemia, liver enzyme abnormalities, genital tract abnormalities and exocrine pancreatic insufficiency. In addition, patients with 17q12MD also have facial dysmorphism, neuro-developmental and neuropsychiatric disorders. CASE: A 16-year-old girl with obesity and mild facial dysmorphism was admitted to the hospital with symptoms of diabetes that started two days prior to her admission. She was diagnosed with severe diabetic ketoacidosis and treated accordingly. She had been followed up with the diagnoses of multicystic renal disease, hydronephrosis, hepatosteatosis, hypomagnesemia and hyperuricemia since the age of six. She had mild intellectual disability. Her menarche started two months ago. Cranial magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy and a partial empty sella. Her mother had diabetes, hypomagnesemia and mild intellectual disability and her maternal grandfather and uncle had diabetes. Her grandfather also had renal cystic disease. All of them are on oral antidiabetic medication. The genetic analysis of the patient and her mother revealed a loss of 1.6 megabases in chromosome 17q12. CONCLUSIONS: MODY5 should be kept in mind in patients with diabetes who present with extra pancreatic findings, especially with renal cystic disease, more over, a genetic analysis including the study of 17q12MD should be carried out in patients who present with additional neuropsychiatric findings. Ketoacidosis can be seen in patients with MODY5. Ketoacidosis and renal anomalies and dysfunction are factors that increase and affect the severity of each other in these patients.

The Clinical Characteristics and Gene Mutations of Maturity-Onset Diabetes of the Young Type 5 in Sixty-One Patients.

Aims: Maturity-onset diabetes of the young type 5 (MODY5), a rare disease, is very easy to be misdiagnosed as type 2 diabetes. To get better understanding of the disease, we analyzed the clinical characteristics and gene mutations of MODY5. Methods: PubMed, Cochrane, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: "MODY5" OR "HNF1B maturity-onset diabetes of the young" OR "maturity-onset diabetes of the young type 5" OR "renal cysts and diabetes syndrome". Clinical characteristics and gene mutations of MODY5 were analyzed. The demography, clinical characteristics, and blood indicators of patients were described utilizing simple summary statistics. Variables were analyzed by t-test, Wilcoxon signed rank test, and Fisher exact test. Spearman's correlation analysis was used for bi-variate analysis. All tests were two-sided, and a p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows (SPSS). Results: A total of 48 literatures were included in this study, including 61 eligible patients and 4 different mutations. Of the 39 patients with available body weight index, 15 (38.46%) were underweight, 21 (53.85%) were normal weight and 3 (7.69%) were overweight or obese. Of the 38 patients with available family history, 25 (65.79%) reported a family history of diabetes. Of the 34 patients with available age of diabetes diagnosis, the median age of diabetes diagnosis was 16.00 years old and 88.24% (30/34) of patients were under 25 years old when they were first diagnosed with diabetes. Renal cysts were presented in 72.41%, hypomagnesemia in 91.67%, and pancreatic dysplasia in 71.88% of the patients. Patients with hepatocyte nuclear factor 1B (HNF1B) deletion had lower serum magnesium, serum creatinine, and higher eGFR than patients with other gene mutations, and the difference was statistically significant. Conclusions: The young onset of diabetes with low or normal BMI, renal cysts, hypomagnesemia, and pancreatic dysplasia should be recommended to genetic testing in order to differentiate MODY5 from other types of diabetes earlier.

Establishment of PLAFMCi005-A induced pluripotent stem cells derived from PBMC from a patient with renal cysts and diabetes syndrome.

Renal cysts and diabetes syndrome (RCAD) is caused by gene mutations in hepatocyte nuclear factor 1-ß (HNF1B), but the underlying molecular mechanism is still unclear. This study established PLAFMCi005-A human induced pluripotent stem cells (iPSCs) by reprogramming peripheral blood mononuclear cells (PBMCs) from an RCAD patient. PLAFMCi005-A has differentiation potential and can be used to investigate the pathogenesis of RCAD caused by HNF1B gene mutations, thus promoting the development of related drugs.

Blood pressure in children with renal cysts and diabetes syndrome.

Cystic kidney diseases such as autosomal recessive or dominant polycystic kidney disease (ARPKD and ADPKD) are associated with high prevalence of arterial hypertension. On the contrary, studies on hypertension in children with renal cysts and diabetes (RCAD) syndrome caused by abnormalities in the HNF1B gene are rare. Therefore, the primary aim of our study was to investigate the prevalence of high blood pressure in children with RCAD syndrome due to HNF1B gene abnormalities and secondary to search for possible risk factors for development of high blood pressure. Data on all children with genetically proven RCAD syndrome from three pediatric nephrology tertiary centers were retrospectively reviewed (office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), creatinine clearance, renal ultrasound, echocardiography, albuminuria/proteinuria). High blood pressure was defined as BP ≥ 95th percentile of the current ESH 2016 guidelines and/or by the use of antihypertensive drugs. Thirty-two children with RCAD syndrome were investigated. Three children received ACE inhibitors for hypertension and/or proteinuria. High blood pressure was diagnosed using office BP in 22% of the children (n = 7). In the 7 performed ABPM, 1 child (14%) was diagnosed with hypertension and one child with white-coat hypertension. Creatinine clearance, proteinuria, albuminuria, body mass index, enlargement, or hypodysplasia of the kidneys and prevalence of HNF1B-gene deletion or mutation were not significantly different between hypertensive and normotensive children.Conclusion: High blood pressure is present in 22% of children with RCAD syndrome. What is Known: • Arterial hypertension is a common complication in children with polycystic kidney diseases. What is New: • High office blood pressure is present in 22% and ambulatory hypertension in 14% of children with renal cyst and diabetes (RCAD) syndrome.

Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model.

Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b ablation leads to more severe phenotypes. We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor site. Unlike heterozygous mice previously characterized, mice heterozygous for the splicing mutation exhibited decreased HNF1B protein levels and bilateral renal cysts from embryonic day 15, originated from glomeruli, early proximal tubules (PTs) and intermediate nephron segments, concurrently with delayed PT differentiation, hydronephrosis and rare genital tract anomalies. Consistently, mRNA sequencing showed that most downregulated genes in embryonic kidneys were primarily expressed in early PTs and the loop of Henle and involved in ion/drug transport, organic acid and lipid metabolic processes, while the expression of previously identified targets upon Hnf1b ablation, including cystic disease genes, was weakly or not affected. Postnatal analyses revealed renal abnormalities, ranging from glomerular cysts to hydronephrosis and, rarely, multicystic dysplasia. Urinary proteomics uncovered a particular profile predictive of progressive decline in kidney function and fibrosis, and displayed common features with a recently reported urine proteome in an RCAD pediatric cohort. Altogether, our results show that reduced HNF1B levels lead to developmental disease phenotypes associated with the deregulation of a subset of HNF1B targets. They further suggest that this model represents a unique clinical/pathological viable model of the RCAD disease.

Insights into the etiology and physiopathology of MODY5/HNF1B pancreatic phenotype with a mouse model of the human disease.

Maturity-onset diabetes of the young type 5 (MODY5) is due to heterozygous mutations or deletion of HNF1B. No mouse models are currently available to recapitulate the human MODY5 disease. Here, we investigate the pancreatic phenotype of a unique MODY5 mouse model generated by heterozygous insertion of a human HNF1B splicing mutation at the intron-2 splice donor site in the mouse genome. This Hnf1bsp2/+ model generated with targeted mutation of Hnf1b mimicking the c.544+1G>T (T) mutation identified in humans, results in alternative transcripts and a 38% decrease of native Hnf1b transcript levels. As a clinical feature of MODY5 patients, the hypomorphic mouse model Hnf1bsp2/+ displays glucose intolerance. Whereas Hnf1bsp2/+ isolated islets showed no altered insulin secretion, we found a 65% decrease in pancreatic insulin content associated with a 30% decrease in total large islet volume and a 20% decrease in total ß-cell volume. These defects were associated with a 30% decrease in expression of the pro-endocrine gene Neurog3 that we previously identified as a direct target of Hnf1b, showing a developmental etiology. As another clinical feature of MODY5 patients, the Hnf1bsp2/+ pancreases display exocrine dysfunction with hypoplasia. We observed chronic pancreatitis with loss of acinar cells, acinar-to-ductal metaplasia, and lipomatosis, with upregulation of signaling pathways and impaired acinar cell regeneration. This was associated with ductal cell deficiency characterized by shortened primary cilia. Importantly, the Hnf1bsp2/+ mouse model reproduces the pancreatic features of the human MODY5/HNF1B disease, providing a unique in vivo tool for molecular studies of the endocrine and exocrine defects and to advance basic and translational research. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist: A case report.

RATIONALE: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. PATIENT CONCERNS: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. DIAGNOSIS: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. INTERVENTIONS: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. OUTCOMES: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. LESSONS: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.

A novel HNF1B mutation p.R177Q in autosomal dominant tubulointerstitial kidney disease and maturity-onset diabetes of the young type 5: A pedigree-based case report.

RATIONALE: Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene result in a very variable presentation, including maturity onset diabetes of the young (MODY), renal cysts, renal dysplasia, and autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by tubular damage, renal fibrosis, and progressive renal dysfunction. PATIENT CONCERNS: A 22-year-old man came to the hospital presenting with hyperglycemia, hyperuricemia and elevated serum creatinine. His urine protein was within the normal range. The ultrasound examination revealed shrunken kidneys with renal cysts. The patient's mother was diagnosed with diabetes mellitus when she was 25 years old. Her laboratory results showed elevated serum creatinine. Her ultrasonography revealed shrunken kidneys with renal cysts and hydronephrosis without kidney stones. The next-generation sequencing revealed that the proband and his mother held the same heterozygous missense mutation (c.530G>A, NM_000458, p.R177Q) in the HNF1B gene. Bioinformatic analyses predicted that the mutation was likely pathogenic. DIAGNOSIS: The patient and his mother were diagnosed as ADTKD and MODY5 due to HNF1B mutation. INTERVENTION: The proband was administered metformin at a dose of 500 mg/day. OUTCOMES: The patient had well-controlled blood glucose levels and a stable renal function at his 12-month follow-up. LESSONS: We should take into account the diagnoses of ADTKD and MODY5 if patients present with early onset diabetes and multiple renal cysts or evidence of renal tubulointerstitial dysplasia, especially those with negative proteinuria results. Genetic testing helps detect the HNF1B gene mutations.

Use of Antibiotics in early Childhood and Dental Enamel Defects in 6- to 12-year-old Children in Primary Health Care / Uso de antibióticos na primeira infância e defeitos de esmalte dentário em crianças de 6 a 12 anos na Atenção Primária à Saúde

ABSTRACT Dental enamel defects (DED) are lesions that occur due several factors. Proper care is needed to promote their treatment and prevention. The aim of this study was to evaluate the occurrence of DED in permanent teeth of children who used antimicrobial drugs in the first four years of life. This is a crosssectional study carried out in a Primary Health Care (PHC) service, which included children from six to 12 years of age. DED were evaluated by oral examination, and data on the use of antimicrobials in early childhood were collected based on medical records. Data were analyzed with the chisquare test and Fisher's exact test. The sample included 144 children. In relation to DED, 50% (72) and 20.1% (29) presented opacity and hypoplasia, respectively. Amoxicillin was the most frequently prescribed drug, followed by sulfamethoxazole + trimethoprim. Among the children, 78.5% (113) were prescribed antimicrobial drugs at least once during the first 4 years of life, and 55% (79) of them presented some type of DED. There was no statistically significant association between the variables analyzed. In conclusion, there was high prevalence of children with DED, and amoxicillin was the most commonly prescribed antibiotic.

RESUMO Os defeitos do esmalte dentário (DED) são lesões que ocorrem devido a vários fatores e é necessária atenção para promover seu tratamento e prevenção. O objetivo foi avaliar a ocorrência de DED em dentes permanentes de crianças que usaram antimicrobianos nos primeiros quatro anos de vida. Tratase de um estudo transversal realizado em um serviço de Atenção Primária à Saúde (APS), que incluiu crianças de seis a 12 anos de idade. A DED foi avaliada por dados de exames bucais, e os dados sobre o uso de antimicrobiano na primeira infância foram coletados com base em prontuários médicos. A análise foi realizada com o teste do quiquadrado e o teste exato de Fisher. A amostra foi composta por 144 crianças. Em relação ao DED, 50%(72) e 20,1%(29) apresentaram opacidade e hipoplasia, respectivamente. A amoxicilina foi o medicamento prescrito com mais freqüência, seguido pelo sulfametoxazol+ trimetoprim. Entre as crianças, 78,5%(113) receberam medica mentos antimicrobianos pelo menos uma vez nos primeiros 4 anos de vida e 55%(79) deles apresentaram algum tipo de DED. Não houve associação estatisticamente significante entre as variáveis analisadas. Em conclusão, houve uma alta prevalência de crianças com DED e a amoxicilina foi o antibiótico mais comumente prescrito.

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NET) in addition to right hydronephrosis due to multiple ureteral bladder carcinomas. She received total right nephrectomy, ureterectomy and partial cystectomy for multiple ureteral bladder carcinomas [non-invasive papillary urothelial carcinoma, low grade (G1), pTa, LV10, u-rtx, RM0, and pN0 (0/8)]. She also received distal pancreatomy for pancreatic NET [NET G1]. She then was referred to our department at age 69 due to increase in her HbA1c value from 6.2 to 7.2%; 75 g oral glucose tolerance test revealed impaired glucose tolerance. Her clinical characteristics (uterus bicornis, pancreas hypoplasia, and renal cysts) closely resembled the phenotype of MODY5, in which mutations in the HNF1B gene have been reported. Our genetic testing failed to detect any mutation or microdeletion in the coding or minimal promoter regions of the HNF1B gene. Although there remains a possibility that genetic mutations in introns and regulatory regions of the HNF1B gene might cause the MODY5-like manifestations in this patient, these results might suggest involvement of genes other than HNF1B in the pathogenesis of our patient's disease.

A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes.

BACKGROUND/OBJECTIVES: Patients referred for HNF1B testing present very heterogeneous phenotypes. Despite suggestive characteristics, many do not harbor mutations in HNF1B. Our objective was to evaluate the clinical characteristics of probands referred for HNF1B genetic testing through a nationwide monogenic diabetes screening program. METHODS: Probands tested for HNF1B mutations in the 2005-2018 period (N = 50) were identified in the Polish Monogenic Diabetes Registry, which prospectively recruits primarily pediatric patients and their families on a nationwide scale. Variants that had been reported pathogenic were reassessed using criteria of the American College of Medical Genetics and Genomics (ACMG). A structured medical interview was performed with all available individuals, their parents, and/or their physicians. For each patient, HNF1B score was calculated based on available clinical information. RESULTS: The study group numbered 36 unrelated probands (28% lost to follow-up): 14 with pathogenic or likely-pathogenic variants in HNF1B, one with a variant of uncertain significance, and 21 negative for HNF1B mutations. Presence of cystic kidneys (OR = 9.17, 95% CI:1.87-44.92), pancreatic abnormalities (OR = 15, 95% CI:1.55-145.23), elevated liver enzymes (OR = 15, 95% CI:1.55-145.23) best discriminated HNF1B-positive cases from the negative ones. Presence of impaired glucose tolerance coupled with kidney disease in the proband and one parent was also highly predictive for HNF1B mutations (OR = 11.11, 95% CI:1.13-109.36). HNF1B-score with recommended cutoff distinguished patients with and without HNF1B findings with 100% sensitivity and 47.6% specificity. Addition of four clinical variables to select patients based on HNF1B score improved specificity to 71.4% (95% CI:47.8%-88.7%) while retaining 100% sensitivity. CONCLUSIONS: Detailed medical interview may enable more accurate patient selection for targeted genetic testing.

Odontodisplasia Regional y Agenesia de Premolares. Reporte de un Caso / Regional Odontodysplasia and Premolar Agenesis. Case Report

RESUMEN: La odontodisplasia regional (OR) es una alteración en el desarrollo, no hereditario y que afecta tanto la dentición temporal como la dentición definitiva. Involucra a los tejidos mesodérmicos y ectodérmicos de los dientes lo que es condescendiente con hallazgos clínicos, radiográficos e histológicos. Su etiología aun es desconocida y se presenta mayoritariamente en mujeres. Clínicamente puede afectar al maxilar, a la mandíbula o ambas arcadas pero generalmente solo se ve comprometida una ellas, principalmente el más afectado es el hueso maxilar. Radiográficamente se observa una pobre diferencia entre los tejidos del esmalte y la dentina, siendo tejidos menos radiopacos que su contraparte sana generando un aspecto descrito como "diente fantasma". Histológicamente se observan zonas hipocalcificadas del esmalte con un orden de prismas irregulares mientras que la dentina se observa con un número reducido de túbulos dentinarios y de consistencia más fibrosa en su zona coronal. El tratamiento de la OR es controversial ya que su incidencia es baja y la literatura al respecto no es clara. El objetivo de este manuscrito, fue reportar un caso de OR y revisar la literatura relacionada. Presentamos un caso de OR en una paciente de 12 años que presenta ausencia de los dientes 2.4, 2.5 y 2.6; restos radiculares y agenesia de los dientes 3.5 y 4.5. Se describirán sus aspectos clínicos, radiográficos e histológicos. Se realizó una búsqueda sistemática en las siguientes bases de datos: Clínical key, Science Direct, PubMed y SciELO.

ABSTRACT: Regional odontodysplasia (RO) is a variation in the development; it is not hereditary and it affects both deciduous and permanent dentition. It involves the mesodermal and ectodermal tissues of dental pieces, and coincides with clinical, radiographic and histological findings. Its etiology is still unknown and it reportedly occurs mostly in women. Clinically it can affect the maxilla, mandible or both arches but generally only one is compromised, mainly the maxilla which is affected the most. Radiographically there is limited difference between enamel and dentin tissue, which is less radiopaque than their healthy counterpart, generating an aspect described as "phantom tooth". Histologically hypocalcified areas of the enamel are observed with an irregular order of prisms while the dentine is observed with a reduced number of dentinal tubules and more fibrous consistency in the coronal area. RO treatment is controversial since its incidence is low and the literature on these events is not clear. The aim of this manuscript was to report a case of RO and review related literature. We present a case of RO in a 12-year-old patient who presents absence of parts 2.4.2.5 and 2.6; radicular remains and agenesis of parts 3.5 and 4.5. Its clinical, radiographic and histological aspects are described. A systematic search was carried out in the following databases: Clinical key, Science Direct, PubMed and SciELO.

Staircase-pattern neonatal line in human deciduous teeth is associated with tooth type.

OBJECTIVE: The staircase (Sc) pattern enamel microstructure is an expression of an impaired ameloblast function. It has been reported to appear in the neonatal line (NNL), the accentuated stria evincing live birth in deciduous tooth enamel. Our objective was to investigate the prevalence of Sc NNL in deciduous tooth types and its possible association with perinatal circumstances. DESIGN: Sc in the NNL of 88 teeth, a collection derived from a long-term, prospectively followed population cohort, was recorded with linear polarised transmitted light and analysed for tooth type, duration and mode of delivery, and pain medication used during labour. RESULTS: Sc prevalence in the NNL differed highly significantly between tooth types (p < 0.0001). An increase in Sc prevalence was significantly associated with an increased ratio of prenatal to total crown enamel (p < 0.001), when buccal and lingual crown walls were analysed separately. No significant association was found between Sc prevalence and duration or mode of delivery or pain-relieving medication (p = 0.57, p = 0.65, p = 0.58, respectively). CONCLUSION: This research indicates that the NNL location within tooth crown enamel has a strong impact on microstructural changes along the NNL. Considering our results of Sc prevalence, deciduous canines, having the least Sc appearance, could be used in studies that aim to investigate factors associated with NNL width. In addition, Sc prevalence variation in first deciduous molars might enable to investigation of physiological stressors strong enough to cause ameloblast impairment, such as Sc.