Analysis of the IDS Gene in 38 Patients with Hunter Syndrome: The c.879G>A (p.Gln293Gln) Synonymous Variation in a Female Create Exonic Splicing

BACKGROUND: Hunter syndrome (mucopolysaccharidosis type II, MPS II) is a rare disease inherited in an X-linked autosomal recessive pattern. It is the prevailing form of the mucopolysaccharidoses in China. Here we investigated mutations of IDS (iduronate 2-sulfatase) gene in 38 unrelated Chinese patients, one of which is a female. METHODS: Peripheral leucocytes were collected from the patients and the IDS gene was amplified to looking for the variations. For a female patient, the X chromosome status was analyzed by androgen receptor X-inactivation assay and the mutation impact on RNA level was further performed by reverse transcription polymerase chain reaction. RESULTS: We discovered that point mutations constituted the major form while mutations in codon p.R468 defined the largest number of patients in our cohort. Consistent with data from other ethnic groups, exons 9 and 3 had comparatively more mutations, while exon 2 had quite a few mutations unique to Chinese patients. Of the 30 different mutations identified, only 9 were novel: one was a premature termination mutation, i.e., c.196C>T (p.Gln66X); three were missense mutations, i.e., c.200T>C (p.Leu67Pro), c.215T>C (p.Leu72Pro), c.389C>T (p.Thr130Ile); one was a small deletion, i.e., c.1104_1122del19 (p.Ser369ArgfsX16); and one was a deletion that spanned both exons 8 and 9 deletion leading to gross structural changes in the IDS gene. In addition, a synonymous mutation c.879G>A (p.Gln293Gln) was identified in a female Hunter disease patient, which resulted in loss of the original splicing site, activated a cryptic splicing site upstream, leading to a 28 bp deletion and a premature termination at p. Tyr285GlufsX47. Together with concurrent skewed X-inactivation this was believed to facilitate the development of Hunter disease in this girl. CONCLUSIONS: In conclusion, the molecular analysis of IDS gene in Chinese patients confirmed the Hunter disease diagnosis and expanded the mutation and clinical spectrum of this devastating disorder

Sources of variability in computed tomography perfusion: implications for acute stroke management

Object. Although dynamic, first-pass cerebral CT perfusion is used in the evaluation of acute ischemic stroke, a lack of standardization restricts the value of this imaging modality in clinical decision-making. The purpose of this study was to comprehensively review the reported sources of variability and error in cerebral CT perfusion results. Methods. A systematic literature review was conducted, 120 articles were reviewed, and 23 published original research articles were included. Sources of variability and error were thematically categorized and presented within the context of the 3 stages of a typical CT perfusion study: data acquisition, postprocessing, and results interpretation. Results. Seven factors that caused variability were identified and described in detail: 1) contrast media, the iodinated compound injected intravascularly to permit imaging of the cerebral vessels; 2) data acquisition rate, the number of images obtained by CT scan per unit time; 3) user inputs, the subjective selections that operators make; 4) observer variation, the failure of operators to repeatedly measure a perfusion parameter with precision; 5) software operational mode, manual, semiautomatic, or automatic; 6) software design, the mathematical algorithms used to perform postprocessing; and 7) value type, absolute versus relative values. Conclusions. Standardization at all 3 stages of the CT perfusion study cycle is warranted. At present, caution should be exercised when interpreting CT perfusion results as these values may vary considerably depending on a variety of factors. Future research is needed to define the role of CT perfusion in clinical decision-making for acute stroke patients and to determine the clinically acceptable limits of variability in CT perfusion results. (DOI: 10.3171/2011.3.FOCUS1136

Reliability of visual assessment of non-contrast CT, CT angiography source images and CT perfusion in patients with suspected ischemic stroke

Contains fulltext : 125853.pdf (publisher's version ) (Open Access)BACKGROUND AND PURPOSE: Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke. METHODS: We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement. RESULTS: Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps. CONCLUSION: Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging