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1.  Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech 
Background
Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS.
Methods
As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker’s speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development.
Results
Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent.
Conclusions
Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of this pediatric motor speech disorder with multiple genes, pathways and complex interactions. We also submit that our findings illustrate the potential use of WES for both gene identification and case-by-case clinical diagnostics in pediatric motor speech disorders.
doi:10.1186/1866-1955-5-29
PMCID: PMC3851280  PMID: 24083349
Apraxia of speech; Developmental verbal dyspraxia; Next-generation sequencing; Speech disorder; Whole-exome sequencing
2.  Natural history of minimal aortic injury following blunt thoracic aortic trauma 
Canadian Journal of Surgery  2012;55(6):377-381.
Background
Endovascular repair of blunt traumatic thoracic aortic injuries (BTAI) is common at most trauma centres, with excellent results. However, little is known regarding which injuries do not require intervention. We reviewed the natural history of untreated patients with minimal aortic injury (MAI) at our centre.
Methods
We conducted a retrospective database review to identify all patients with a BTAI between October 2008 and March 2010. The cohort comprised patients initially untreated because of the lesser degree of injury of an MAI. We reviewed initial and follow-up computed tomography (CT) scans and clinical information.
Results
We identified 69 patients with a BTAI during the study period; 10 were initially untreated and were included in this study. Degree of injury included intimal flaps (n = 7, 70%), pseudoaneurysms with minimal hematoma (n = 2, 20%) and circumferential intimal tear (n = 1, 10%). Six (60%) patients were male, and the median age was 40 years. Duration of clinical follow-up ranged from 1 month to 6 years (median 2 mo) after discharge, whereas CT radiologic follow-up ranged from 1 week to 6 years (median 6 wk). Seven (70%) patients had complete resolution or stabilization of their MAI, 1 (10%) with circumferential intimal tear showed extension of the injury at 8 weeks postinjury and underwent successful repair, and 2 (20%) were lost to follow-up.
Conclusion
There appears to be a subset of patients with BTAI who require no surgical intervention. This includes those with limited intimal flaps, which often resolve. Radiologic surveillance is mandatory to ensure MAI resolution and identify any progression that might prompt repair.
doi:10.1503/cjs.007311
PMCID: PMC3506686  PMID: 22992400
4.  Late conversion of endovascular to open repair of abdominal aortic aneurysms 
Canadian Journal of Surgery  2012;55(4):254-258.
Background
Failure of endovascular repair (EVAR) of an abdominal aortic aneurysm can result in significant risk of morbidity and mortality. We review our experience with late conversions to open repair.
Methods
We conducted a retrospective database review to identify all EVAR procedures performed between 1997 and 2010 and the number converted to open repair at our university-affiliated medical centre. Late conversion was defined as those occurring at least 30 days after initial EVAR.
Results
In all, 892 EVARs took place during the study period. Six patients (0.7%) required late conversion to open repair. Their mean age was 71 (range 58–83) years, and half were women. Half of the initial EVARs were for ruptured aneurysms. The median time to conversion was 15.6 (range 1.7–61.3) months. Indications for secondary conversion (50% urgent, 50% elective) included persistent type I endoleak (n = 3), combined type II and III endoleak (n = 1), graft thrombosis (n = 1) and aneurysm rupture (n = 1). Supraceliac clamping was required in most patients (67%), and the mean transfusion requirement was 2.6 units. Total endograft explantation occurred in 2 patients (33%), whereas partial or total endograft preservation occurred in 4 (67%). Median length of stay in hospital after conversion was 7 (range 6–73) days. There were no instances of early or in-hospital mortality following conversion.
Conclusion
Our EVAR experience includes a low rate of late conversion to open repair, with most conversions being a result of persistent aneurysm perfusion. Although technically challenging, late conversion can be safe. Our experience supports ongoing surveillance after EVAR.
doi:10.1503/cjs.038310
PMCID: PMC3404146  PMID: 22617542
5.  The effect of patient transfer on outcomes after rupture of an abdominal aortic aneurysm 
Canadian Journal of Surgery  2007;50(1):43-47.
Objective
Centralization of vascular surgery services has resulted in patients being transferred longer distances for treatment of life-threatening conditions. The purpose of this study was to determine whether patient transfer adversely affects the survival of people with a ruptured abdominal aortic aneurysm (RAAA).
Methods
We performed a retrospective review of all patients undergoing attempted repair of an RAAA at our centre, over a recent 3.5-year period (August 2000–December 2003). Patients were divided into those presenting directly to our centre and those transferred from another hospital. The main outcome variable was in-hospital or 30-day mortality, with secondary variables including time to surgical treatment, mortality in the first 24 hours and length of hospitalization.
Results
Eighty-one patients (73% men) underwent attempted open repair of an RAAA at our centre during this period. Twenty-four patients (29.6%) presented directly to our hospital, while 57 (70.4%) were transferred from another institution. The overall mortality rate was 53%. Although transferred patients took twice as long as direct patients to get to the operating room (6.3 v. 3.2 h, p = 0.03), there was no difference in mortality between the 2 groups (50% v. 54%, p = ns). However, deaths of transferred patients were more likely to occur in the first 24 postoperative hours, compared with direct patients (40% v. 33%, p < 0.05). Neither mean intensive care unit stay (5.8 and 8.1 d) nor total hospitalization (20.9 and 18.8 d) differed between the 2 groups.
Conclusions
Although the transfer of patients with RAAA results in a treatment delay, it does not adversely affect the already high mortality rates associated with this condition. These results may be attributed to a preselection of patients who are able to tolerate such a delay.
PMCID: PMC2384251  PMID: 17391616

Results 1-5 (5)