Dataset Information

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

ABSTRACT: To assess the frequency of mutations in C19orf12 in the greater neurodegeneration with brain iron accumulation (NBIA) population and further characterize the associated phenotype.Samples from 161 individuals with idiopathic NBIA were screened, and C19orf12 mutations were identified in 23 subjects. Direct examinations were completed on 8 of these individuals, and medical records were reviewed on all 23. Histochemical and immunohistochemical studies were performed on brain tissue from one deceased subject.A variety of mutations were detected in this cohort, in addition to the Eastern European founder mutation described previously. The characteristic clinical features of mitochondrial membrane protein-associated neurodegeneration (MPAN) across all age groups include cognitive decline progressing to dementia, prominent neuropsychiatric abnormalities, and a motor neuronopathy. A distinctive pattern of brain iron accumulation is universal. Neuropathologic studies revealed neuronal loss, widespread iron deposits, and eosinophilic spheroidal structures in the basal ganglia. Lewy neurites were present in the globus pallidus, and Lewy bodies and neurites were widespread in other areas of the corpus striatum and midbrain structures.MPAN is caused by mutations in C19orf12 leading to NBIA and prominent, widespread Lewy body pathology. The clinical phenotype is recognizable and distinctive, and joins pantothenate kinase-associated neurodegeneration and PLA2G6-associated neurodegeneration as one of the major forms of NBIA.

SUBMITTER: Hogarth P

PROVIDER: S-EPMC3589182 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

Hogarth Penelope P Gregory Allison A Kruer Michael C MC Sanford Lynn L Wagoner Wendy W Natowicz Marvin R MR Egel Robert T RT Subramony S H SH Goldman Jennifer G JG Berry-Kravis Elizabeth E Foulds Nicola C NC Hammans Simon R SR Desguerre Isabelle I Rodriguez Diana D Wilson Callum C Diedrich Andrea A Green Sarah S Tran Huong H Reese Lindsay L Woltjer Randall L RL Hayflick Susan J SJ

Neurology 20121226 3

<h4>Objective</h4>To assess the frequency of mutations in C19orf12 in the greater neurodegeneration with brain iron accumulation (NBIA) population and further characterize the associated phenotype.<h4>Methods</h4>Samples from 161 individuals with idiopathic NBIA were screened, and C19orf12 mutations were identified in 23 subjects. Direct examinations were completed on 8 of these individuals, and medical records were reviewed on all 23. Histochemical and immunohistochemical studies were performed ...[more]

PMID: 23269600

Similar Datasets

Project description:PurposeTo describe carpet lesions (laterally spreading tumors ≥ 3 cm) detected at computed tomographic (CT) colonography, including their clinical, imaging, and pathologic features.Materials and methodsThe imaging reports for 9152 consecutive adults undergoing initial CT colonography at a tertiary center were reviewed in this HIPAA-compliant, institutional review board-approved retrospective study to identify all potential carpet lesions detected at CT colonography. Carpet lesions were defined as morphologically flat, laterally spreading tumors 3 cm or larger. For those patients with neoplastic carpet lesions, CT colonography studies were analyzed to determine maximal lesion width and height, oral contrast material coating, segmental location, and computer-aided detection (CAD) findings. Demographic data and details of clinical treatment in these patients were reviewed.ResultsEighteen carpet lesions in 18 patients (0.2%; mean age, 67.1 years; eight men, 10 women) were identified and were subsequently confirmed at colonoscopy and pathologic examination among 20 potential flat masses (≥3 cm) prospectively identified at CT colonography (there were two nonneoplastic rectal false-positive findings). No additional neoplastic carpet lesions were found in the cohort undergoing colonoscopy after CT colonography and/or surgery (there were no false-negatives). Mean lesion width was 46.5 mm (range, 30-80 mm); mean lesion height was 7.9 mm (range, 4-14 mm). Surface retention of oral contrast material was noted in all 18 cases. All but two lesions were located in the distal rectosigmoid or proximal right colon. At CAD, 17 (94.4%) lesions were detected (mean, 6.2 CAD marks per lesion). Sixteen lesions (88.9%) demonstrated advanced histologic features, including a villous component (n = 11), high-grade dysplasia (n = 4), and invasive cancer (n = 5). Sixteen patients (88.9%) required surgical treatment for complete excision.ConclusionCT colonography can effectively depict carpet lesions. Common features in this series included older patient age, rectal or cecal location, surface coating with oral contrast material, multiple CAD hits, advanced yet typically benign histologic features, and surgical treatment.

Project description:INTRODUCTION: Osteoarthritis (OA) is considered to be a multifactorial and polygenic disease and diagnosis is mainly clinical and radiological. Correlation between radiographic data and clinical status has been reported. However, very few studies, especially in Caucasian people, describe the association between the Kellgren and Lawrence OA grading scale (KL) and genetic alterations to better understand OA etiopathogenesis and susceptibility. In order to update the knee OA grading, in this study we assessed the associations between KL grade, clinical features such as American Knee Society Score (AKSS), age, and polymorphisms in the principal osteoarthritis susceptibility (OS) genes in Sicilian individuals. METHODS: In 66 Sicilian individuals affected by primary knee OA, the clinical and radiographic evaluation was performed using 2 sub-scores of AKSS (knee score (KS) and function score (FS)) and KL. The patients were also classified according to age. Online Mendelian Inheritance in Man (OMIM) and Database of Single Nucleotide Polymorphisms (dbSNP) Short Genetic Variations databases were used to select gene regions containing the following polymorphisms to analyze: FRZB rs288326 and rs7775, MATN3 rs77245812, ASPN D14 repeats, PTHR2 rs76758470, GDF5 rs143383 and DVWA rs11718863. Patient genotypes were obtained using Sanger DNA sequencing analysis. RESULTS: In our cohort of patients a statistical association between the variables analyzed was reported in all associations tested (KL versus KS, FS and age). We observed that a mild to severe OA radiographic grade is related to severe clinical conditions and loss of articular function and that the severity of symptoms increases with age. Concerning the genotyping analysis, our results revealed a significant statistical association between KL grading and GDF5 rs143383 and DVWA rs11718863 genetic alterations. The latter was also associated with a more severe radiographic grade, displaying its predictive role as OA marker progression. Statistically significant association between clinical, radiographic and genetic signs observed, suggests extending the actual grading of knee OA based mainly on X-ray features. CONCLUSIONS: This work represents a multidisciplinary and translational medicine approach to study OA where clinical, radiological, and OS5 and OS6 SNPs evaluation could contribute to better define grading and progression of OA and to the development of new therapies.

Dataset Information

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

Publications

New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets