Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience

• Published in: Hong Kong medical journal = Xianggang yi xue za zhi 2018-08, Vol.24 (4), p.340-349
• Main Authors: Mak, C M, Chen, S Pl, Mok, N S, Siu, W K, Lee, H Hc, Ching, C K, Tsui, P T, Fong, N C, Yuen, Y P, Poon, W T, Law, C Y, Chong, Y K, Chan, Y W, Yung, T C, Fan, K Yy, Lam, C W
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged, 80 and over; Cardiac arrhythmia; Cardiomyopathies - diagnosis; Cardiomyopathies - genetics; Cardiomyopathy; Channelopathies - diagnosis; Channelopathies - genetics; Child; Electrocardiography; Families & family life; Family medical history; Female; Genes; Genetic Testing - statistics & numerical data; Genetics; Heterozygote; Hong Kong; Humans; Infant; Long QT syndrome; Male; Middle Aged; Mutation; Phenotype; Young Adult
• ISSN: 1024-2708; 2226-8707
• DOI: 10.12809/hkmj176870

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. Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: and for long QT syndrome; for Brugada syndrome; for catecholaminergic polymorphic ventricular tachycardia; and for hypertrophic cardiomyopathy; for dilated cardiomyopathy; and and for arrhythmogenic right ventricular dysplasia/cardiomyopathy. 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 (NM_198056.2:c.429del and c.2024-11T>A), two in (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in (NM_170707.3:c.73C>A and c.1209_1213dup). 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.