Genetic Testing Yield and Clinical Characteristics of Hypertrophic Cardiomyopathy in Understudied Ethnic Groups: Insights From a New Zealand National Registry.

BACKGROUND: Aotearoa/New Zealand has a multiethnic population. Patients with hypertrophic cardiomyopathy (HCM) are enrolled in the national Cardiac Inherited Diseases Registry New Zealand. Here, we report the characteristics of Cardiac Inherited Diseases Registry New Zealand HCM probands with and without pathogenic or likely pathogenic (P/LP) genetic variants for HCM, and assess genetic testing yield and variant spectrum by self-identified ethnicity. METHODS: Probands with HCM and enrolled in Cardiac Inherited Diseases Registry New Zealand who have undergone clinical genetic testing over a 17-year period were included. Clinical data, family history, and genetic test results were analyzed. RESULTS: Of 336 probands, 121 (36%) were women, 220 (66%) were European ethnicity, 41 (12%) were Maori, 26 (8%) were Pacific people, and 49 (15%) were other ethnicities. Thirteen probands (4%) presented with sudden death and 19 (6%) with cardiac arrest. A total of 134 (40%) had a P/LP variant identified; most commonly in the MYBPC3 gene (60%) followed by the MYH7 gene (24%). A P/LP variant was identified in 27% of Maori or Pacific probands versus 43% European or other ethnicity probands (P=0.022); 16% of Maori or Pacific probands had a variant of uncertain significance identified, compared with 9% of European or other ethnicity probands (P=0.092). Women more often had a P/LP variant identified than men (48% versus 35%; P=0.032), and variant-positive probands were younger at clinical diagnosis than variant of uncertain significance/variant-negative probands (39±17 versus 50±17 years; P<0.001) and more likely to have experienced cardiac arrest or sudden death events over their lifetime (P=0.002). CONCLUSIONS: Carriage of a P/LP variant in HCM probands is associated with presentation at younger age, and cardiac arrest or sudden death events. Maori or Pacific probands were less likely to have a P/LP variant identified than European or other ethnicity probands.

Threats to the emotional wellbeing of mainland Chinese students studying in Australia: an interpretivist study.

PURPOSE: In 2017, international students contributed almost $32 billion to Australia's economy, more than half of which was attributable to students from China. Despite its historical popularity as a study destination, research suggests that these students confront numerous obstacles in pursuing their studies within Australia. In this study, the perspectives of these students were explored. The dominant issues raised by these students related to mental health and emotional wellbeing. METHODS: Nineteen students in one Australian university participated in one-on-one in-depth semi-structured interviews. Data were analysed using grounded theory approaches. Three broad themes were generated in the study: psychological stress (which was linked to language barriers, shifts in pedagogy, and changes in lifestyle); perceived safety (which was linked to lack of security, safety and perceived racial discrimination); and social isolation (linked to reduced sense of belonging; lacking close personal connections; and feelings of loneliness and homesickness). CONCLUSIONS: Results suggested that a tripartite model of interactive risk factors may be appropriate for exploring how international students fare emotionally with their new environments.

Genetic testing in Polynesian long QT syndrome probands reveals a lower diagnostic yield and an increased prevalence of rare variants.

BACKGROUND: New Zealand has a multiethnic population and a national cardiac inherited disease registry (Cardiac Inherited Disease Registry New Zealand [CIDRNZ]). Ancestry is reflected in the spectrum and prevalence of genetic variants in long QT syndrome (LQTS). OBJECTIVE: The purpose of this study was to study the genetic testing yield and mutation spectrum of CIDRNZ LQTS probands stratified by self-identified ethnicity. METHODS: A 15-year retrospective review of clinical CIDRNZ LQTS probands with a Schwartz score of ≥2 who had undergone genetic testing was performed. RESULTS: Of the 264 included LQTS probands, 160 (61%) reported as European, 79 (30%) NZ Maori and Pacific peoples (Polynesian), and 25 (9%) Other ethnicities, with comparable clinical characteristics across ethnic groups (cardiac events in 72%; age at presentation 28±19 years; corrected QT interval 512±55 ms). Despite comparable testing (5.3±1.4 LQTS genes), a class III-V LQTS variant was identified in 35% of Polynesian probands as compared with 63% of European and 72% of Other probands (P<.0001). Among variant-positive CIDRNZ LQTS probands (n=148), Polynesians were more likely to have non-missense variants (57% vs 39% and 25% in probands of European and Other ethnicity, respectively; P=.005) as well as long QT syndrome type 1-3 variants not reported elsewhere (71% vs European 22% and Other 28%; P<.0001). Variants found in multiple probands were more likely to be shared within the same ethnic group; P<.01). CONCLUSION: Genetic testing of Polynesian LQTS probands has a lower diagnostic yield, despite comparable testing and clinical disease severity. Rare LQTS variants are more common in Polynesian LQTS probands. These data emphasize the importance of increasing the knowledge of genetic variation in the Polynesian population.

Long QT molecular autopsy in sudden unexplained death in the young (1-40 years old): Lessons learnt from an eight year experience in New Zealand.

BACKGROUND: To review long QT syndrome molecular autopsy results in sudden unexplained death in young (SUDY) between 2006 and 2013 in New Zealand. METHODS: Audit of the LQTS molecular autopsy results, cardiac investigations and family screening data from gene-positive families. RESULTS: During the study period, 365 SUDY cases were referred for molecular autopsy. 128 cases (35%) underwent LQTS genetic testing. 31 likely pathogenic variants were identified in 27 cases (21%); SCN5A (14/31, 45%), KCNH2 (7/31, 22%), KCNQ1 (4/31, 13%), KCNE2 (3/31, 10%), KCNE1 (2/31, 7%), KCNJ2 (1/31, 3%). Thirteen variants (13/128, 10%) were ultimately classified as pathogenic. Most deaths (63%) occurred during sleep. Gene variant carriage was more likely with a positive medical history (mostly seizures, 63% vs 36%, p = 0.01), amongst females (36% vs 12%, p = 0.001) and whites more than Maori (31% vs 0, p = 0.0009). Children 1-12 years were more likely to be gene-positive (33% vs 14%, p = 0.02). Family screening identified 42 gene-positive relatives, 18 with definitive phenotypic expression of LQTS/Brugada. 76% of the variants were maternally inherited (p = 0.007). Further family investigations and research now support pathogenicity of the variant in 13/27 (48%) of gene-positive cases. CONCLUSION: In New Zealand, variants in SCN5A and KCNH2, with maternal inheritance, predominate. A rare variant in LQTS genes is more likely in whites rather than Maori, females, children 1-12 years and those with a positive personal and family history of seizures, syncope or SUDY. Family screening supported the diagnosis in a third of the cases. The changing classification of variants creates a significant challenge.

Detection of sudden death syndromes in New Zealand.

AIM: To investigate regional variations in the detection of sudden death syndromes across New Zealand by assessing registrations in the national Cardiac Inherited Diseases Registry New Zealand (CIDRNZ). METHODS: The CIDRNZ has been a national entity since 2009, with a hub in Auckland and locally funded regional coordinators (Midland, Central) linked with multidisciplinary cardiac genetic teams. Registration is consent-based and voluntary, and involves the collection of clinical/genetic information and permits genetic testing and research. Registry data were extracted from the CIDRNZ in October 2015 and results are expressed as registrations per 100,000 people by district health board area. RESULTS: The CIDRNZ has 1,940 registrants from 712 families, 46% of whom are definitely or probably affected by cardiac inherited disease. There are clear regional differences in registration frequencies between regions and between the North and South Islands, both for overall registrations (56/100,000 and 14/100,000, respectively; p<0.001) and for long QT syndrome registrations (15/100,000 and 6/100,000, respectively; p<0.001). Regions with local coordinators have the highest number of registrations. CONCLUSION: The detection of sudden death syndromes in New Zealand through a cardiac genetic registry is possible but much work is needed to improve regional variation in the detection/reporting of these conditions across the country.

Inpatient detection of cardiac-inherited disease: the impact of improving family history taking.

OBJECTIVES: 'Idiopathic' cardiac conditions such as dilated cardiomyopathy (DCM) and resuscitated sudden cardiac death (RSCD) may be familial. We suspected that inpatient cardiology services fail to recognise this. Our objective was to compare diagnostic value of family histories recorded by inpatient cardiology teams with a multigenerational family tree obtained by specially trained allied professionals. METHODS: 2 experienced cardiology nurses working in 2 tertiary adult cardiac units were trained in cardiac-inherited diseases and family history (FHx) taking, and established as regional coordinators for a National Cardiac Inherited Disease Registry. Over 6 months they sought 'idiopathic' cardiology inpatients with conditions with a possible familial basis, reviewed the FHx in the clinical records and pursued a minimum 3-generation family tree for syncope, young sudden death and cardiac disease (full FHx). RESULTS: 37 patients (22 males) were selected: mean age 51 years (range 15-79). Admission presentations included (idiopathic) RSCD (14), dyspnoea or heart failure (11), ventricular tachycardia (2), other (10). 3 patients had already volunteered their familial diagnosis to the admitting team. FHx was incompletely elicited in 17 (46%) and absent in 20 (54%). 29 patients (78%) provided a full FHx to the coordinator; 12 of which (41%) were strongly consistent with a diagnosis of a cardiac-inherited disease (DCM 7, hypertrophic cardiomyopathy 3, long QT 1, left ventricular non-compaction 1). Overall, a familial diagnostic rate rose from 3/37(8%) to 12/37 (32%). CONCLUSIONS: Adult cardiology inpatient teams are poor at recording FHx and need to be reminded of its powerful diagnostic value.