Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype-Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT. Hum Mutat 33: 949-959, 2012. (C) 2012 Wiley Periodicals, Inc.

Charcot foot: Skin temperature as a good clinical parameter for predicting disease outcome

Twenty-eight diabetics presenting with acute Charcot foot were immobilized and the temperature difference between limbs measured at each month. All patients had monthly follow-up visits for a year and the relapse rate was zero. We found that skin temperature is a good parameter to ensure safe immobilization withdrawal. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Transcriptional response to GAA deficiency (Pompe disease) in infantile-onset patients

Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease. (C) 2012 Elsevier Inc. All rights reserved.

Multiple Tooth Agenesis in Non-syndromic Patient: a rare case report

Dental agenesis is a term referred to the absence of one or more teeth. However, oligodontia is a severe type of tooth agenesis involving six or more congenitally missing teeth, excluding the third molars. Oligodontia has a low prevalence and is a very rare condition. The aim was to show this case report of a 13-year-old female patient who presented oligodontia with absence of eight permanent teeth and condylar atrophy on left side. The patient had no history of any syndrome or systemic disease according to the anamnesis. Is very important to know oligodontia features to perform a carefully treatment plan.

Dentomaxillofacial manifestations of Gaucher's disease: preliminary clinical and radiographic findings

Objectives: A wide variety of manifestations is presented in patients with Gaucher's disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient's group with an age-sex matched control group; and to correlate clinical and radiological data. Methods: Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient's records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher's exact test). Results: Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed. Conclusions: A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients. Dentomaxillofacial Radiology (2012) 41, 541-547. doi: 10.1259/dmfr/143023353

Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation

Periodontitis comprises a group of multifactorial diseases in which periodontopathogens accumulate in dental plaque and trigger host chronic inflammatory and immune responses against periodontal structures, which are determinant to the disease outcome. Although unusual cases of non-inflammatory destructive periodontal disease (NIDPD) are described, their pathogenesis remains unknown. A unique NIDPD case was investigated by clinical, microbiological, immunological and genetic tools. The patient, a non-smoking dental surgeon with excessive oral hygiene practice, presented a generalized bone resorption and tooth mobility, but not gingival inflammation or occlusion problems. No hematological, immunological or endocrine alterations were found. No periodontopathogens (A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola) or viruses (HCMV, EBV-1 and HSV-1) were detected, along with levels of IL-1 beta and TNF-alpha in GCF compatible with healthy tissues. Conversely ALP, ACP and RANKL GCF levels were similar to diseased periodontal sites. Genetic investigation demonstrated that the patient carried some SNPs, as well HLA-DR4 (*0404) and HLA-B27 alleles, considered risk factors for bone loss. Then, a less vigorous and diminished frequency of toothbrushing was recommended to the patient, resulting in the arrest of alveolar bone loss, associated with the return of ALP, ACP and RANKL in GCF to normality levels. In conclusion, the unusual case presented here is compatible with the previous description of NIDPD, and the results that a possible combination of excessive force and frequency of mechanical stimulation with a potentially bone loss prone genotype could result in the alveolar bone loss seen in NIDPD.

An epidemiological scoring system for tooth wear and dental erosive wear

Background: The prevalence and severity of tooth wear and dental erosion is rising in children and there is no consensus about an index to be employed. Aim: To assess the reliability of an epidemiological scoring system dental wear index (DWI) to measure tooth wear and dental erosive wear. Design: An epidemiological cross-sectional survey was conducted to evaluate and compare tooth wear and dental erosion using the dental wear index and erosion wear index (EWI). The study was conducted with randomised samples of 2,371 children aged between 4 years and 12 years selected from the State of São Paulo, Brazil. Records were used for calculating tooth wear and dental erosion; the incisal edge and canine cusp were excluded. Results: As the schoolchildren's ages increased the severity of primary tooth wear increased in canines (P = 0.0001, OR = 0.34) and molars (P = 0.0001, OR = 2.47) and erosion wear increased in incisal/occlusal (P = 0.0001, OR = 5.18) and molars (P = 0.0001, OR = 2.47). There was an increased prevalence of wear in the permanent teeth of older schoolchildren, particularly on the incisal/occlusal surfaces (P = 0.0001, OR = 7.03). Conclusion: The prevalence of tooth wear and dental erosion increased as age increased in children. The epidemiological scoring system Dental Wear Index is able to measure both tooth wear and dental erosive wear. This index should be used to monitor the progression of non-carious lesions and to evaluate the levels of disease in the population.