A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome.

Rett syndrome is caused by mutations in the gene MECP2 in approximately 80% of affected individuals. We describe a previously unknown MeCP2 isoform. Mutations unique to this isoform and the absence, until now, of identified mutations specific to the previously recognized protein indicate an important role for the newly discovered molecule in the pathogenesis of Rett syndrome.

Computed tomography identified factors that preclude living kidney donation.

INTRODUCTION: The purpose of this study was to determine the variety and prevalence of renal and non-renal abnormalities detected on multidetector computed tomography (MDCT) that precluded patients from donating a kidney. METHODS: Institutional review board approval was obtained and the requirement for informed consent was waived. A retrospective, single-centre review of 701 patients (444 female, 257 male; age range 18-86 years; mean age 43.2±11.9 years) that underwent renal donor protocol MDCT was conducted. A systematic review of the CT report, records from multidisciplinary renal transplantation rounds, and electronic medical records was performed to determine which patients were approved or declined as live renal donors. If declined as a donor, CT-identified reasons were categorized as abnormalities of renal vasculature, renal parenchyma, collecting system, or extra-renal. RESULTS: A total of 81 patients were excluded as renal donors on the basis of CT findings. Abnormalities of the collecting system accounted for the most frequent cause of exclusion (n=41), with asymptomatic renal calculi being detected in 39 patients. Complex vascular anatomy and vascular abnormalities resulted in the exclusion of 29 patients. Supernumerary arteries and early arterial branching resulted in the exclusion of 20 patients, while renal vein anomalies leading to exclusion were uncommon (n=2). Abnormalities of renal parenchyma resulted in the exclusion of nine patients. Three patients were diagnosed with autosomal dominant polycystic kidney disease, two patients had renal cell carcinoma, and two patients had areas of cortical scarring. A complex cystic lesion requiring surveillance imaging was encountered in one patient and a large area of renal infarction related to prior adrenalectomy was demonstrated in one patient. Extra-renal abnormalities leading to exclusion were limited to two patients with pulmonary nodules. CONCLUSIONS: MDCT plays a critical role in the preoperative assessment of potential renal donors by identifying contraindications to donor nephrectomy and providing accurate vascular mapping. This study is anticipated to be informative for those involved in the workup of potential living renal donors by quantifying the incidence and reasons for donor exclusion identified on CT.

Early-stage clear cell tubulopapillary renal cell carcinoma: imaging features and distinction from clear cell and papillary subtypes.

PURPOSE: Clear cell tubulopapillary renal cell carcinoma (CCTPRCC) is a recently described, low-grade subtype of renal cancer. We determined if imaging features could be used to distinguish early-stage CCTPRCC from stage-matched clear cell RCC (ccRCC) and papillary RCC (pRCC). METHODS: This IRB-approved retrospective study included 54 stage T1a patients with pathologically confirmed CCTPRCC (n = 18), ccRCC (n = 18), and pRCC (n = 18). CT (n = 48) and MRI (n = 27) exams were reviewed and imaging features compared. Continuous variables were evaluated using ANOVA and Tukey's multiple comparison tests. Categorical variables were compared using Chi-square test or Fisher's exact test. RESULTS: Compared to pRCC, CCTPRCC had a lower mean attenuation value on unenhanced CT (p < 0.017), was more often hyperintense on T2-weighted images (p < 0.0001), showed an ill-defined margin (p = 0.003), and demonstrated nonenhancing areas (p = 0.0003). The presence of all three of these statistically significant features [hypoattenuation (unenhanced attenuation ≤25 HU), ill-defined margin, nonenhancing areas] yielded an area under the receiver operator curve (ROC) of 0.92 (95% CI 0.83-0.99) for differentiating CCTPRCC from pRCC. There were no significant differences in the imaging features of CCTPRCC and ccRCC. CONCLUSIONS: Early-stage clear cell tubulopapillary renal cell carcinoma can be distinguished from papillary RCC based on low attenuation on unenhanced CT, high intensity on T2-weighted images, an ill-defined margin, and presence of nonenhancing areas, but cannot be distinguished from clear cell RCC.

Peer Review in Radiology: A Resident and Fellow Perspective.

PURPOSE: The purpose of this study was to explore Canadian radiology residents' and fellows' understanding, attitudes, opinions, and preferences toward peer review. METHODS: An Internet-based anonymous questionnaire designed to understand one's familiarity, attitudes, opinions, and preferences toward peer review was distributed to radiology residents and fellows across Canada. Data were analyzed using descriptive statistics, and answers were stratified by level of training. RESULTS: A total of 136 trainees responded to the survey with 92 completed survey responses available for descriptive statistics. Approximately half of respondents are familiar with peer review (49%), and 39% of trainees are involved in peer review. Most respondents (92%) expressed an interest in learning more about peer review; believe that it should be incorporated into the residency training curriculum (86%), be mandatory (72%), and that current participation will increase odds of future participation (91%). Most trainees (80%) are comfortable advising one another about errors, but less comfortable advising staff (21%). CONCLUSIONS: Residents and fellows welcome the opportunity to learn more about peer review and believe it should be incorporated into the residency training curriculum. Understanding the attitudes and perceptions held by trainees regarding peer review is important, as a means to optimize education and maximize current and future participation in peer review.

MRI for pelvic floor dysfunction: can the strain phase be eliminated?

PURPOSE: The purpose of the study was to determine if the strain phase of an MR defecography (MRD) protocol is redundant and can be eliminated without a loss of diagnostic information. MATERIALS AND METHODS: Institutional review board approval was obtained and the requirement for informed consent was waived. A retrospective single-center review of 80 MRD examinations (68 female, 12 male, mean age 55 years old) was conducted. Two radiologists blinded to patient information evaluated in consensus the strain and evacuation phases separately and in a random order. Each phase was assessed for the presence and degree of posterior compartment descent, cystocele, urethral hypermobility, uterovaginal prolapse, rectocele, rectal intussusception, and enterocele. The degree of pelvic floor descent was compared using a paired t test and McNemar's test was used to compare the proportion of abnormal findings. RESULTS: The evacuation phase identified all abnormalities identified on the strain phase and also identified both additional and more pronounced abnormalities, including an additional 34 cystoceles, 20 cases of urethral hypermobility, 13 uterovaginal prolapses, 36 rectoceles, 5 rectal intussusceptions, and 6 enteroceles (all p < 0.02). The mean posterior compartment descent was 24.1 mm greater on the evacuation phase than the strain phase (p < 0.0001). CONCLUSION: The strain phase is redundant and we propose that it can be eliminated from a routine MRD protocol. This will help streamline the examination, simplify patient instructions, and reduce both imaging and reporting time.

Clinical stringency greatly improves mutation detection in Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder of girls, caused by mutations in the X-linked MECP2 gene. Worldwide recognition of the RTT clinical phenotype in the early 1980's allowed many cases to be diagnosed, and established RTT as one of the most common mental retardation syndromes in females. The years since then led to a refinement of the phenotype and the recent elaboration of Revised Diagnostic Criteria (RDC). Here, we study the impact of the presence versus the absence of the use of diagnostic criteria from the RDC to make a diagnosis of RTT on MECP2 mutation detection in Canadian patients diagnosed and suspected of having RTT. METHODS: Using dHPLC followed by sequencing in all exons of the MECP2 gene, we compared mutation detection in a historic cohort of 35 patients diagnosed with RTT without the use of specific diagnostic criteria to a separate more recent group of 101 patients included on the basis of strict fulfillment of the RDC. RESULTS: The MECP2 mutation detection rate was much higher in subjects diagnosed using a strict adherence to the RDC (20% vs. 72%). CONCLUSIONS: These results suggest that clinical diagnostic procedures significantly influence the rate of mutation detection in RTT, and more generally emphasize the importance of diagnostic tools in the assessment of neurobehavioral syndromes.

Sequence variants within exon 1 of MECP2 occur in females with mental retardation.

A new splice variant of the Rett syndrome gene, MECP2, was recently identified, that includes coding sequence from exon 1, and is the predominant transcript in the central nervous system. This sequence encodes polyalanine and polyglycine stretches within the N-terminal portion of MeCP2, and may confer novel functional properties to the protein. We screened autism, mental retardation (MR), and control populations for sequence variation within this region, and identified variation in approximately 1% of MR cases screened (N = 1,410). No variants were identified in the autism sample (N = 401). Most of these variants occur within a trinucleotide repeat region and result in change in number of alanine or glycine residues within the repeat stretches. We suggest some of these variants may be a relatively frequent cause of non-specific MR or developmental delay.