C M Mak1, S Pl Chen2, N S Mok3, W K Siu2, H Hc Lee2, C K Ching2, P T Tsui3, N C Fong4, Y P Yuen2, W T Poon2, C Y Law2, Y K Chong2, Y W Chan2, T C Yung5, K Yy Fan6, C W Lam7. 1. Chemical Pathology Laboratory, Kowloon West Cluster Laboratory Genetic Service, Department of Pathology, Princess Margaret Hospital, Laichikok, Hong Kong. 2. Department of Pathology, Princess Margaret Hospital, Laichikok, Hong Kong. 3. Department of Medicine, Princess Margaret Hospital, Laichikok, Hong Kong. 4. Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Laichikok, Hong Kong. 5. Department of Paediatric Cardiology, Queen Mary Hospital, Pokfulam, Hong Kong. 6. Department of Cardiac Medicine, Grantham Hospital, Wong Chuk Hang, Hong Kong. 7. Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong.
Abstract
INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.
INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.
Entities:
Keywords:
Cardiomyopathies; Channelopathies; Genetic association studies
Authors: Anand N Ganesan; Carlos G Vanoye; Ferdous Alam; Kathryn E Waddell-Smith; Andrew D McGavigan; Gemma Correnti; Eric Haan; Alex Brown; Jamie Vandenberg; Alfred L George Journal: Circ Genom Precis Med Date: 2020-01-31
Authors: Gary Tse; Sharen Lee; Tong Liu; Ho Chuen Yuen; Ian Chi Kei Wong; Chloe Mak; Ngai Shing Mok; Wing Tak Wong Journal: Front Physiol Date: 2020-09-18 Impact factor: 4.566