Judith MacCormick
Boston Children's Hospital
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Featured researches published by Judith MacCormick.
Heart Rhythm | 2008
Carey-Anne Eddy; Judith MacCormick; Seo-Kyung Chung; Jackie Crawford; Donald R. Love; Mark I. Rees; Jonathan R. Skinner; Andrew N. Shelling
BACKGROUND Sequencing or denaturing high-performance liquid chromatography (dHPLC) analysis of the known genes associated with the long QT syndrome (LQTS) fails to identify mutations in approximately 25% of subjects with inherited LQTS. Large gene deletions and duplications can be missed with these methodologies. OBJECTIVE The purpose of this study was to determine whether deletions and/or duplications of one or more exons of the main LQTS genes were present in an LQTS mutation-negative cohort. METHODS Multiplex ligation-dependent probe amplification (MLPA), a quantitative fluorescent approach, was used to screen 26 mutation-negative probands with an unequivocal LQTS phenotype (Schwartz score >4). The appropriate MLPA kit contained probes for selected exons in LQTS genes KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2. Real-time polymerase chain reaction was used to validate the MLPA findings. RESULTS Altered exon copy number was detected in 3 (11.5%) patients: (1) an ex13-14del of the KCNQ1 gene in an 11-year-old boy with exercise-induced collapse (QTc 580 ms); (2) an ex6-14del of the KCNH2 gene in a 22-year-old woman misdiagnosed with epilepsy since age 9 years (QTc 560 ms) and a sibling with sudden death at age 13 years; and (3) an ex9-14dup of the KCNH2 gene in a 12 year-old boy (QTc 550 ms) following sudden nocturnal death of his 32-year-old mother. CONCLUSION If replicated, this study demonstrates that more than 10% of patients with LQTS and a negative current generation genetic test have large gene deletions or duplications among the major known LQTS susceptibility genes. As such, these findings suggest that sequencing-based mutation detection strategies should be followed by deletion/duplication screening in all LQTS mutation-negative patients.
Circulation-arrhythmia and Electrophysiology | 2009
Tao Yang; Seo-Kyung Chung; Wei Zhang; Jonathan G. L. Mullins; Caroline H. McCulley; Jackie Crawford; Judith MacCormick; Carey–Anne Eddy; Andrew N. Shelling; John K. French; Ping Yang; Jonathan R. Skinner; Dan M. Roden; Mark I. Rees
Background—Inherited long-QT syndrome is characterized by prolonged QT interval on the ECG, syncope, and sudden death caused by ventricular arrhythmia. Causative mutations occur mostly in cardiac potassium and sodium channel subunit genes. Confidence in mutation pathogenicity is usually reached through family genotype-phenotype tracking, control population studies, molecular modeling, and phylogenetic alignments; however, biophysical testing offers a higher degree of validating evidence. Methods and Results—By using in vitro electrophysiological testing of transfected mutant and wild-type long-QT syndrome constructs into Chinese hamster ovary cells, we investigated the biophysical properties of 9 KCNQ1 missense mutations (A46T, T265I, F269S, A302V, G316E, F339S, R360G, H455Y, and S546L) identified in a New Zealand–based long-QT syndrome screening program. We demonstrate through electrophysiology and molecular modeling that 7 of the missense mutations have profound pathological dominant-negative loss-of-function properties, confirming their likely disease-causing nature. This supports the use of these mutations in diagnostic family screening. Two mutations (A46T, T265I) show suggestive evidence of pathogenicity within the experimental limits of biophysical testing, indicating that these variants are disease-causing via delayed- or fast-activation kinetics. Further investigation of the A46T family has revealed an inconsistent cosegregation of the variant with the clinical phenotype. Conclusions—Electrophysiological characterization should be used to validate long-QT syndrome pathogenicity of novel missense channelopathies. When such results are inconclusive, great care should be taken with genetic counseling and screening of such families, and alternative disease-causing mechanisms should be considered.
Child Abuse & Neglect | 2009
Patrick Kelly; Judith MacCormick; Rebecca Strange
OBJECTIVES To describe the outcome of referral to the statutory authorities for infants under 2 years with non-accidental head injury (NAHI), and to establish whether the authorities held sufficient information to develop a risk profile for these cases. METHODS Retrospective review of cases admitted to hospital in Auckland, New Zealand from 1988 to 1998. Records from the hospital admission, child protective services and Police were reviewed, up to 19 years from diagnosis. RESULTS Of 39 infants, 33 survived to leave hospital. Documentation of risk factors was erratic, and sometimes incongruent between agencies. Inter-agency case conferences took place in 17/39 (44%). The Department of Child, Youth and Family Services (CYF) used an informal family agreement to secure safety in 15/33 survivors (45%). Family Group Conferences occurred in 17/33 (52%). Nine of 33 were placed permanently outside the home (27%), two (6%) with unrelated caregivers. Charges were laid in 18/39 cases (46%). Fifteen cases came to trial, with 14 convictions (36%). Of the survivors, 44% were later renotified to CYF. There was no obvious relationship between type of intervention and re-notification. CONCLUSIONS Ensuring the safety of an infant with NAHI, and identifying and taking appropriate action with regard to the offender, are complex tasks. In New Zealand, data collection is often incomplete and inter-agency practice and collaboration is variable. Although the rate of prosecution was relatively high by international standards, many children were later notified again for further concerns of abuse or neglect, suggesting that our interventions have been only partially successful. PRACTICE IMPLICATIONS This paper suggests that all infants admitted to hospital with non-accidental head injury should become part of a prospective inter-agency research study, using a standardised data collection instrument. This should include the systematic collection of all data known or suspected to be associated with risk of child abuse, and incorporate long-term prospective follow-up, regardless of child protective or legal outcomes. Without large numbers followed prospectively and according to sound methodology, it is difficult to prove which forms of intervention are better than others at reducing the risk of further abuse.
Heart Lung and Circulation | 2011
Judith MacCormick; Jackie Crawford; Seo-Kyung Chung; Andrew N. Shelling; Cary-Anne Evans; Mark I. Rees; Warren M. Smith; Ian G. Crozier; Hugh McAlister; Jon R. Skinner
BACKGROUND It is often reported that clinical symptoms are useful in differentiating cardiac from non-cardiac syncope. Studies in the young are rare. This study was designed to capture the symptoms and signs reported by patients with cardiac syncope before the patients or their attending clinicians knew the final diagnosis. METHODS Retrospective case-note review of 35 consecutive unrelated gene-positive probands with a proven cardiac channelopathy. RESULTS The presentation leading to diagnosis of cardiac channelopathy was resuscitated sudden cardiac death in 7 patients; syncope in 20; collapse with retained consciousness in 2; palpitations in 1 and an incidental finding in 5. For the 20 patients with syncope (LQTS 18, Brugada syndrome 2), median age at presentation was 13.9 years (1.8 day to 40.8 years). Of the 17 patients able to describe the onset of syncope, 11 (65%) had at least one symptom prior to collapse, though none reported nausea. Dizziness or lightheadedness was the most frequent symptom, being experienced by 8 (47%). Nine (of 20) patients (45%) had witnessed seizure-like activity and 8 (40%) had urinary incontinence. Nineteen patients were capable of describing the post-syncopal period, of whom 15 (79%) reported symptoms, the most common (12; 65%) being drowsiness or exhaustion. CONCLUSIONS Cardiac syncope in the young frequently presents with symptoms and signs that are typically associated with other causes of transient loss of consciousness, including vasovagal syncope and seizure disorders. The presence of symptoms may not be as helpful in differentiating arrhythmic from non-arrhythmic events as is often supposed. A thorough history, appropriate investigations and a high index of suspicion remain essential in the assessment of syncope.
The Annals of Thoracic Surgery | 2010
Julia D. Flint; Thomas L. Gentles; Judith MacCormick; Heather Spinetto; A. Kirsten Finucane
BACKGROUND Neonatal repair of interrupted aortic arch (IAA) involves an early choice between a single-stage or two-stage strategy. Risk factors for each are not yet fully investigated, especially as they relate to major associated cardiac malformations. We aimed to assess the outcome of neonates undergoing biventricular repair of IAA and associated congenital heart defects. METHODS Preoperative assessment, operative management, and outcome were retrospectively reviewed for 18 consecutive patients undergoing biventricular IAA repair at Starship Childrens Hospital from 2000 to 2005. RESULTS Seventeen patients underwent a single-stage procedure and one patient weighing 970 g underwent a two-stage procedure. All but one had a ventricular septal defect. Major associated cardiac defects were present in 7 and included aortopulmonary window (1), truncus arteriosus (3), transposition of the great arteries (1), and aortic valve atresia (2). Those with major associated cardiac defects had longer procedural times but similar early mortality and intensive care unit and hospital stay. One patient required a pacemaker for complete heart block. Mean follow-up was 4.5 years with one late death and all survivors reporting normal functional status. Developmental delay was present in 5 (27%), 4 of whom had 22q deletion. Late reoperation was required in 4, including two Konno procedures and two pulmonary conduit changes. CONCLUSIONS A good functional outcome and low reoperation rate can be achieved with a single-stage repair regardless of the presence of major additional cardiac abnormalities. Neonates with risk factors such as low birth weight and prematurity require an individualized approach.
Circulation-arrhythmia and Electrophysiology | 2009
Tao Yang; Seo-Kyung Chung; Wei Zhang; Jonathan G. L. Mullins; Caroline H. McCulley; Jackie Crawford; Judith MacCormick; Carey-Anne Eddy; Andrew N. Shelling; John K. French; Ping Yang; Jonathan R. Skinner; Dan M. Roden; Mark I. Rees
Background—Inherited long-QT syndrome is characterized by prolonged QT interval on the ECG, syncope, and sudden death caused by ventricular arrhythmia. Causative mutations occur mostly in cardiac potassium and sodium channel subunit genes. Confidence in mutation pathogenicity is usually reached through family genotype-phenotype tracking, control population studies, molecular modeling, and phylogenetic alignments; however, biophysical testing offers a higher degree of validating evidence. Methods and Results—By using in vitro electrophysiological testing of transfected mutant and wild-type long-QT syndrome constructs into Chinese hamster ovary cells, we investigated the biophysical properties of 9 KCNQ1 missense mutations (A46T, T265I, F269S, A302V, G316E, F339S, R360G, H455Y, and S546L) identified in a New Zealand–based long-QT syndrome screening program. We demonstrate through electrophysiology and molecular modeling that 7 of the missense mutations have profound pathological dominant-negative loss-of-function properties, confirming their likely disease-causing nature. This supports the use of these mutations in diagnostic family screening. Two mutations (A46T, T265I) show suggestive evidence of pathogenicity within the experimental limits of biophysical testing, indicating that these variants are disease-causing via delayed- or fast-activation kinetics. Further investigation of the A46T family has revealed an inconsistent cosegregation of the variant with the clinical phenotype. Conclusions—Electrophysiological characterization should be used to validate long-QT syndrome pathogenicity of novel missense channelopathies. When such results are inconclusive, great care should be taken with genetic counseling and screening of such families, and alternative disease-causing mechanisms should be considered.
Circulation-arrhythmia and Electrophysiology | 2009
Tao Yang; Seo-Kyung Chung; Wei Zhang; Jonathan G. L. Mullins; Caroline H. McCulley; Jackie Crawford; Judith MacCormick; Carey-Anne Eddy; Andrew N. Shelling; John K. French; Ping Yang; Jonathan R. Skinner; Dan M. Roden; Mark I. Rees
Background—Inherited long-QT syndrome is characterized by prolonged QT interval on the ECG, syncope, and sudden death caused by ventricular arrhythmia. Causative mutations occur mostly in cardiac potassium and sodium channel subunit genes. Confidence in mutation pathogenicity is usually reached through family genotype-phenotype tracking, control population studies, molecular modeling, and phylogenetic alignments; however, biophysical testing offers a higher degree of validating evidence. Methods and Results—By using in vitro electrophysiological testing of transfected mutant and wild-type long-QT syndrome constructs into Chinese hamster ovary cells, we investigated the biophysical properties of 9 KCNQ1 missense mutations (A46T, T265I, F269S, A302V, G316E, F339S, R360G, H455Y, and S546L) identified in a New Zealand–based long-QT syndrome screening program. We demonstrate through electrophysiology and molecular modeling that 7 of the missense mutations have profound pathological dominant-negative loss-of-function properties, confirming their likely disease-causing nature. This supports the use of these mutations in diagnostic family screening. Two mutations (A46T, T265I) show suggestive evidence of pathogenicity within the experimental limits of biophysical testing, indicating that these variants are disease-causing via delayed- or fast-activation kinetics. Further investigation of the A46T family has revealed an inconsistent cosegregation of the variant with the clinical phenotype. Conclusions—Electrophysiological characterization should be used to validate long-QT syndrome pathogenicity of novel missense channelopathies. When such results are inconclusive, great care should be taken with genetic counseling and screening of such families, and alternative disease-causing mechanisms should be considered.
Heart Rhythm | 2007
Seo-Kyung Chung; Judith MacCormick; Caroline H. McCulley; Jackie Crawford; Carey-Anne Eddy; Edwin A. Mitchell; Andrew N. Shelling; John K. French; Jonathan R. Skinner; Mark I. Rees
/data/revues/01960644/v54i1/S0196064409001139/ | 2013
Judith MacCormick; Hugh McAlister; Jackie Crawford; John K. French; Ian Crozier; Andrew N. Shelling; Carey-Anne Eddy; Mark I. Rees; Jonathan R. Skinner
Heart Lung and Circulation | 2007
Judith MacCormick; Hugh McAlister; Jackie Crawford; John K. French; Ian Crozier; Andrew N. Shelling; C. Nel; Mark I. Rees; Jon R. Skinner