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Background

Heterozygous NKX2-1 loss-of-function variants cause combinations of hyperkinetic movement disorders (MDs, particularly childhood-onset chorea), pulmonary dysfunction, and hypothyroidism. Mobile element insertions (MEIs) are potential disease-causing structural variants whose detection in routine diagnostics remains challenging.

Objective

To establish the molecular diagnosis of two first-degree relatives with clinically suspected NKX2-1-related disorder who had negative NKX2-1 Sanger (SS), whole-exome (WES), and whole-genome (WGS) sequencing.

Methods

The proband's WES was analyzed for MEIs. A candidate MEI in NKX2-1 underwent optimized SS after plasmid cloning. Functional studies exploring NKX2-1 haploinsufficiency at RNA and protein levels were performed.

Results

A 347-bp AluYa5 insertion with a 65-bp poly-A tail followed by a 16-bp duplication of the pre-insertion wild-type sequence in exon 3 of NKX2-1 (ENST00000354822.7:c.556_557insAlu541_556dup) segregated with the disease phenotype.

Conclusions

We identified a de novo exonic AluYa5 insertion causing NKX2-1-related disorder in SS/WES/WGS-negative cases, suggesting that MEI analysis of short-read sequencing data or targeted long-read sequencing could unmask the molecular diagnosis of unsolved MD cases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.  相似文献   
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Breast specimen radiography: evaluation of a compression device   总被引:1,自引:0,他引:1  
Chilcote  WA; Davis  GA; Suchy  P; Paushter  DM 《Radiology》1988,168(2):425-427
The irregular shape and uneven tissue thickness of excised breast specimens makes radiographic evaluation difficult, especially when calcifications are not present. Xeroradiographs before and after compression of 20 separate excised breast specimens were compared, and 17 of the same specimens were compared after compression combined with immersion in water. Specimen compression improved visibility of the lesion on average in 88% of cases, and visibility was equal in 12%. Combined compression/immersion further improved visibility of the lesion on average in 37% of cases. More significantly, evaluation of the compressed specimen led to a change in interpretation of the radiographs in 45% of cases. Compression of the specimen in specimen radiography is recommended in all cases in which pre-biopsy localization is performed.  相似文献   
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Speech-controlled generation of radiology reports   总被引:1,自引:0,他引:1  
Voice entry has been successfully employed to generate radiology reports with a word recognizer with a 1,000-word lexicon capacity. About 50% of reports were able to be dictated with a single 900-word lexicon. This was split into five sections by anatomic or subspecialty application. Each was augmented to 900 words. By switching from one lexicon to another, it was possible to dictate more than 70% of reports. With exclusive use of three lexicons in subspecialty areas (gastrointestinal radiology, neuroradiology, and mammography), and with further modification of the respective vocabulary, it has been possible to employ the system 88% of the time. Twelve percent of cases included wording that was beyond the scope of the lexicon. Computer subsets that allow different translations of some words when used in different contexts have been used. Some of these are used as triggers that will print whole lines, sentences, or even complete reports. Dictation times with voice entry take about 20% longer. Recognition reliability has been greater than 95%.  相似文献   
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Dementia is a frequent and disabling complication of Parkinson's disease (PD). Clinicians and researchers lack a biomarker capable of tracking the structural and functional changes that underlie the evolution of cognitive dysfunction in PD. Magnetic resonance imaging (MRI) has been adopted as a biomarker in natural history and interventional studies of Alzheimer's disease (AD) and amnestic mild cognitive impairment (MCI), but its utility as a biomarker for PD and Parkinson's disease dementia (PDD) is unclear. In this review, the authors summarize the studies that have used MRI to investigate cognitive decline in PD, outline limitations of those studies, and suggest directions for future research. PD dementia is associated with extensive cortical atrophy, which may be quantified with structural MRI. More promisingly, patterns of atrophy may be present in those who have PD with MCI (PD‐MCI). Subcortical white matter tract degeneration is detectable early in the disease with diffusion tensor imaging and may precede changes observed on conventional structural MRI. Although less well studied, other MR techniques, such as functional MRI, MR perfusion imaging with arterial spin labeling, and MR spectroscopy, have demonstrated differences in activation and metabolism between PD and PDD. In this review, the ability to compare studies was limited by the heterogeneity of study populations, cognitive testing methods, and imaging protocols. Future work should adopt agreed scan protocols, should be adequately powered, and should use carefully phenotyped patients to fully maximize the contribution of MRI as a biomarker for PDD. © 2013 Movement Disorder Society  相似文献   
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