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1.
Cardiology ; 137(3): 188-192, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28441660

RESUMO

OBJECTIVE: Cardiomyopathy (CMP) in children is a clinically and genetically heterogeneous group of disorders. Disease-associated mutations have been identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA processing gene, ELAC2, were reported to be associated with the recessively inherited form of hypertrophic CMP (HCM). This study is aimed at describing the cardiac phenotype and outcome of ELAC2 mutation. METHODS: We performed whole exome sequencing followed by targeted mutation screening to identify the genetic etiology of severe infantile-onset CMP in 64 consanguineous Saudi families. RESULTS: A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected in 16 families. The index cases presented between 2 and 7 months of age with HCM in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7 infants (44%). All infants died with a median age of death of 4 months. Almost 1/3 of them died during the initial presentation. CONCLUSION: Our study suggests screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown etiology, especially in the presence of pericardial effusion. Our work demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2 gene; a correlation that helps in counseling parents and in planning appropriate medical intervention.


Assuntos
Cardiomiopatia Dilatada/genética , Cardiomiopatia Hipertrófica/genética , Proteínas de Neoplasias/genética , Saúde da Família , Feminino , Homozigoto , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Fenótipo , Arábia Saudita
2.
Mol Cytogenet ; 11: 9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29416564

RESUMO

BACKGROUND: Quick genetic diagnosis of a patient with congenital heart disease (CHD) is quite important for proper health care and management. Copy number variations (CNV), chromosomal imbalances and rearrangements have been frequently associated with CHD. Previously, due to limitations of microscope based standard karyotyping techniques copious CNVs and submicroscopic imbalances could not be detected in numerous CHD patients. The aim of our study is to identify cytogenetic abnormalities among the selected CHD cases (n = 17) of the cohort using high density oligo arrays. RESULTS: Our screening study indicated that six patients (~35%) have various cytogenetic abnormalities. Among the patients, only patient 2 had a duplication whereas the rest carried various deletions. The patients 1, 4 and 6 have only single large deletions throughout their genome; a 3.2 Mb deletion on chromosome 7, a 3.35 Mb deletion on chromosome 3, and a 2.78 Mb a deletion on chromosome 2, respectively. Patients 3 and 5 have two deletions on different chromosomes. Patient 3 has deletions on chromosome 2 (2q24.1; 249 kb) and 16 (16q22.2; 1.8 Mb). Patient 4 has a 3.35 Mb an interstitial deletion on chromosome 3 (3q13.2q13.31).Based on our search on the latest available literature, our study is the first inclusive array CGH evaluation on Saudi cohort of CHD patients. CONCLUSIONS: This study emphasizes the importance of the arrays in genetic diagnosis of CHD. Based on our results the high resolution arrays should be utilized as first-tier diagnostic tool in clinical care as suggested before by others. Moreover, previously evaluated negative CHD cases (based on standard karyotyping methods) should be re-examined by microarray based cytogenetic methods.

3.
Heart Rhythm ; 14(8): 1191-1199, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28438721

RESUMO

BACKGROUND: Congenital long QT syndrome (LQTS) is an inherited, potentially fatal arrhythmogenic disorder. At least 16 genes have been implicated in LQTS; the yield of genetic analysis of 3 genes (KCNQ1, KCNH2, and SCN5A) is about 70%, with KCNQ1 mutations accounting for ∼50% of positive cases. LQTS is mostly inherited in an autosomal dominant pattern. Systemic analysis of LQTS has not been previously conducted in a population with a high degree of consanguinity. OBJECTIVES: To describe the clinical and molecular profiles of LQTS in the highly consanguineous Saudi population. METHODS: Fifty-six Saudi families with LQTS were consecutively recruited and evaluated. Sequencing of KCNQ1, KCNH2, and SCN5A genes was conducted on all probands, followed by screening of family relatives. RESULTS: Genetic analysis was positive in 32 (57.2%) families, with mutations in KCNQ1 identified in 28 families (50%). Surprisingly, 17 (53.1%) probands were segregating homozygous mutations. Family screening identified 123 individuals with mutations; 89 (72.4%) were heterozygous, 23 (18.7%) were homozygous, and 11 (8.9%) were compound heterozygous. Compared to heterozygous, the phenotype was more severe in homozygous individuals, with cardiac symptoms in 78.3% (vs 12.4%), family history of sudden death in 64.7% (vs 44.4%), and prolonged QT interval in 100% (vs 43.8%). Congenital deafness was found in 11 (47.8%) homozygous probands. CONCLUSION: Our study provides insight into the clinical and molecular profiles of LQTS in a consanguineous population. It underscores the importance of preemptive management in homozygous patients with LQTS and the value of clinical and molecular screening of at-risk relatives.


Assuntos
Consanguinidade , Testes Genéticos/métodos , Síndrome do QT Longo/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Heterozigoto , Homozigoto , Humanos , Incidência , Lactente , Recém-Nascido , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Taxa de Sobrevida/tendências , Adulto Jovem
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