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Ajay Bahl

Publications and source records attributed to Ajay Bahl.

8 recordsLinked to original sources
PubMed2005

Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: natural history.

OBJECTIVES: The aim of this study was to investigate the clinical expression of adenosine monophosphate-activated protein kinase (AMPK) gene mutations (PRKAG2) in adenosine monophosphate (AMP) kinase disease based on 12 years follow-up of known mutation carriers and to define the prevalence of PRKAG2 mutations in hypertrophic cardiomyopathy (HCM). BACKGROUND: Adenosine monophosphate-activated protein kinase gene mutations cause HCM with Wolff-Parkinson-White syndrome and conduction disease. METHODS: Clinical evaluation of 44 patients with known AMP kinase disease was analyzed. Mutation analysis of PRKAG2 was performed by fluorescent single-strand confirmation polymorphism analysis and direct sequencing of abnormal conformers in 200 patients with HCM. RESULTS: Only one additional mutation was identified. The mean age at clinical diagnosis in the 45 gene carriers was 24 years (median 20 years, range 9 to 55 years). Symptoms of palpitation, dypspnea, chest pain, or syncope were present in 31 (69%) gene carriers; 7 (15%) complained of myalgia and had clinical evidence of proximal myopathy. Skeletal muscle biopsy showed excess mitochondria and ragged red fibers with minimal glycogen accumulation. Disease penetrance defined by typical electrocardiogram abnormalities was 100% by age 18 years. Thirty-two of 41 adults (78%) had left ventricular hypertrophy (LVH) on echocardiography, and progressive LVH was documented during follow-up. Survival was 91% at a mean follow-up of 12.2 years. Progressive conduction disease required pacemaker implantation in 17 of 45 (38%) at a mean age of 38 years. CONCLUSIONS: The AMP kinase disease is uncommon in HCM and is characterized by progressive conduction disease and cardiac hypertrophy and includes extracardiac manifestations such as a skeletal myopathy, consistent with a systemic metabolic storage disease. Defects in adenosine triphosphate utilization or in specific cellular substrates, rather than mere passive deposition of amylopectin, may account for these clinical features.

AMP-Activated Protein Kinases↗
PubMed2004

Frequency and clinical expression of cardiac troponin I mutations in 748 consecutive families with hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to evaluate the potential utility of genetic diagnosis in clinical management of families with hypertrophic cardiomyopathy (HCM) caused by mutations in the gene for cardiac troponin I (TNNI3). BACKGROUND: Knowledge about the clinical disease expression of sarcomeric gene mutations in HCM has predominantly been obtained by investigations of single individuals (probands) or selected families. To establish the role of genetic diagnosis in HCM families, systematic investigations of probands and their relatives are needed. METHODS: Cardiac troponin I was investigated by direct sequencing and fluorescent (F)-SSCP analysis in 748 consecutive HCM families. Relatives of HCM probands with TNNI3 mutations were invited for cardiovascular and genetic assessment. RESULTS: The prevalence of TNNI3 mutations was 3.1%. Mutations appeared to cluster in exons 7 and 8. A total of 100 mutation carriers were identified in 23 families with 13 different mutations (6 novel). Disease penetrance was 48%. Patients were diagnosed from the second to eighth decade of life. The morphologic spectrum observed represented a wide range of HCM. Two offspring of clinically unaffected mutation carriers were resuscitated from cardiac arrest, and an additional four individuals died suddenly as their initial presentation. Six individuals experienced other disease-related deaths. CONCLUSIONS: The clinical expression of TNNI3 mutations was very heterogeneous and varied both within and between families with no apparent mutation- or gene-specific disease pattern. The data suggest that disease development may be monitored by regular assessment of cardiac symptoms and electrocardiographic abnormalities. Genetic diagnosis of TNNI3 is valuable in identifying clinically unaffected mutation carriers at risk of disease development and facilitates accurate management and counseling.

Adolescent↗
PubMed2004

Severe disease expression of cardiac troponin C and T mutations in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: We performed genetic investigations of cardiac troponin T (TNNT2) and troponin C (TNNC1) in 235 consecutive patients with idiopathic dilated cardiomyopathy (DCM) to evaluate prevalence of mutations and associated disease expression in affected families. BACKGROUND: Recently, mutations in sarcomeric genes have been reported in DCM. However, the prevalence, penetrance, and clinical significance of sarcomere gene mutations in large consecutive cohorts of DCM patients are poorly defined. METHODS: Mutation detection was performed by fluorescent SSCP/DHPLC analysis and direct sequencing. The functional effects of mutations on interactions within the troponin complex were assessed by a two-hybrid luciferase assay. RESULTS: A total of 43% (102 of 235) of the study cohort had familial DCM. One TNNC1 and four TNNT2 (three novel) mutations were identified in one and four families, respectively. The prevalence of TNNC1/TNNT2 mutations in familial DCM was 5% with a penetrance of 100%. A total of 21 mutation carriers were identified; 6 underwent cardiac transplantation, 5 died of heart failure, and 4 died suddenly at a mean age of 29 years, while 6 remained stable on medication. Functional studies showed significant impairment of mutated troponin interaction compared with wild-type control, indicating an altered regulation of myocardial contractility. CONCLUSIONS: Cardiac troponin C was identified as a novel DCM gene. The disease expression associated with TNNC1 and TNNT2 mutations was severe with complete penetrance. The data suggest that mutation analysis of the troponin complex in DCM patients may prove valuable in early identification of individuals with an adverse prognosis and a high risk of premature death. This may lead to improved management and survival.

Adolescent↗
PubMedDate not supplied

Transcatheter closure of aortopulmonary window.

Aortopulmonary window is an uncommon congenital cardiac defect. Most infants presenting with aortopulmonary window will require conventional surgical repair. Experience with transcatheter closure of aortopulmonary window is limited. We report the case of a 9-year-old girl with aortopulmonary window, in whom transcatheter closure was performed successfully using Amplatzer ductal occluder device.

Aortopulmonary Septal Defect↗