Mutations in CCDC39 and CCDC40 are the Major Cause of Primary Ciliary Dyskinesia with Axonemal Disorganization and Absent Inner Dynein Arms

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder caused by cilia and sperm dysmotility. About 12% of cases show perturbed 9+2 microtubule cilia structure and inner dynein arm (IDA) loss, historically termed “radial spoke defect.” We sequenced CCDC39 and CCDC40 in 54 “radial spoke defect” families, as these are the two genes identified so far to cause this defect. We discovered biallelic mutations in a remarkable 69% (37/54) of families, including identification of 25 (19 novel) mutant alleles (12 in CCDC39 and 13 in CCDC40). All the mutations were nonsense, splice, and frameshift predicting early protein truncation, which suggests this defect is caused by “null” alleles conferring complete protein loss. Most families (73%; 27/37) had homozygous mutations, including families from outbred populations. A major putative hotspot mutation was identified, CCDC40 c.248delC, as well as several other possible hotspot mutations. Together, these findings highlight the key role of CCDC39 and CCDC40 in PCD with axonemal disorganization and IDA loss, and these genes represent major candidates for genetic testing in families affected by this ciliary phenotype. We show that radial spoke structures are largely intact in these patients and propose this ciliary ultrastructural abnormality be referred to as “IDA and microtubular disorganisation defect,” rather than “radial spoke defect.”     

Fusion Viewer: A New Tool for Fusion and Visualization of Multimodal Medical Data Sets

Digital medical images are very easy to be modified for illegal purposes. For example, microcalcification in mammography is an important diagnostic clue, and it can be wiped off intentionally for insurance purposes or added intentionally into a normal mammography. In this paper, we proposed two methods to tamper detection and recovery for a medical image. A 1024 × 1024 x-ray mammogram was chosen to test the ability of tamper detection and recovery. At first, a medical image is divided into several blocks. For each block, an adaptive robust digital watermarking method combined with the modulo operation is used to hide both the authentication message and the recovery information. In the first method, each block is embedded with the authentication message and the recovery information of other blocks. Because the recovered block is too small and excessively compressed, the concept of region of interest (ROI) is introduced into the second method. If there are no tampered blocks, the original image can be obtained with only the stego image. When the ROI, such as microcalcification in mammography, is tampered with, an approximate image will be obtained from other blocks. From the experimental results, the proposed near-lossless method is proven to effectively detect a tampered medical image and recover the original ROI image. In this study, an adaptive robust digital watermarking method combined with the operation of modulo 256 was chosen to achieve information hiding and image authentication. With the proposal method, any random changes on the stego image will be detected in high probability.     

超声图象纹理分析的新方法：—纹理深度法及其实验

本文提出了一种用于B超图象纹理分析的新方法。用此方法可定量计算出有关B超图象纹理的深浅,陡平,疏密或粗细等方面的12个参数,计算机模拟实验结果证实了该方法的可靠性,临床B超图象分析结果表明,该方法有实用价值。     

Functional Cluster Analysis of CT Perfusion Maps: A New Tool for Diagnosis of Acute Stroke?

CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue.     

A splice site and copy number variant responsible for TTC25-related primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia. With few exceptions, PCD is an autosomal recessive condition, and there are over 40 genes associated with the condition. We present a case of a newborn female with clinical features of PCD, specifically the Kartagener syndrome phenotype, due to variants in TTC25. This gene has been previously associated with PCD in three families. Two multi-gene panels performed as a neonate and at two years of age were uninformative. Exome sequencing was performed by the Care4Rare Canada Consortium on a research basis, and an apparent homozygous intronic variant (TTC25:c.1145+1G > A) was identified that was predicted to abolish the canonical splice donor activity of exon 8. The child's mother was a heterozygous carrier of the variant. The paternal sample did not show the splice variant, and homozygosity was observed across the paternal locus. Microarray analysis showed a 50 kb heterozygous deletion spanning the genes TTC25 and CNP. This is the first example of a pathogenic gross deletion in trans with a splice variant, resulting in TTC25-related PCD.