ABSTRACT
The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, genotyping array analysis, and array comparative genomic hybridization on these subjects. The most striking finding was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs impacted on genes of cardiac relevance including RBFOX1, GPC5, KCNRG, CHODL, and GPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not appear to be functionally related. The recognition that SCM predisposition may be associated with a high rate of rare CNVs offers a novel perspective on this enigmatic condition.
Subject(s)
DNA Copy Number Variations , Gene Regulatory Networks , Genotyping Techniques/methods , Takotsubo Cardiomyopathy/genetics , Comparative Genomic Hybridization , Earthquakes , Female , Genetic Predisposition to Disease , Glypicans/genetics , Humans , Lectins, C-Type/genetics , Membrane Proteins/genetics , New Zealand , Oligonucleotide Array Sequence Analysis , Potassium Channels/genetics , RNA Splicing Factors/genetics , Exome SequencingABSTRACT
OBJECTIVE: There are few data on visual outcomes in adulthood of former very low birthweight (VLBW; <1500 g) infants. We aimed to assess vision at 27-29 years in a national cohort of VLBW infants born in 1986 and assessed for retinopathy of prematurity (ROP) when no treatment was available, compared with term born controls. METHODS: The cohort and controls attended a 2-day assessment in Christchurch as part of a larger study. Visual assessment included glasses prescription measured by focimeter, logarithm of the minimum angle of resolution (logMAR) distance visual acuity (VA), contrast sensitivity, autorefraction, retinal photographs and a questionnaire on vision-related everyday activities. Rates of reduced VA and myopia in the VLBW cohort at 27-29 were compared with the results of vision testing at 7-8 years. RESULTS: 250 VLBW adults (77% those alive) gave study consent and 229 (45 with a history of ROP) were assessed in Christchurch, plus 100 term born controls. VLBW adults with ROP had reduced VA compared with no ROP and controls (mean logMAR score (SD); 0.003 (0.19), -0.021 (0.16), -0.078 (0.09), P=0.001). There were no differences in myopia (>2 D) between the groups but high myopia (>5 D) was confined to those with ROP. VLBW adults with ROP drove a car less often and had higher difficulties with everyday activities scores due to eyesight. Between 7-8 and 27-29 years rates of reduced VA were stable but myopia increased. CONCLUSION: Former VLBW young adults with ROP have ongoing problems with vision affecting daily living and should continue in regular ophthalmological review. TRIAL REGISTRATION NUMBER: ACTRN12612000995875, Pre-results .
Subject(s)
Infant, Very Low Birth Weight/physiology , Myopia/physiopathology , Retinopathy of Prematurity/physiopathology , Term Birth , Vision Disorders/physiopathology , Vision, Ocular/physiology , Activities of Daily Living , Adult , Cohort Studies , Contrast Sensitivity/physiology , Female , Follow-Up Studies , Humans , Male , New Zealand , Prospective Studies , Refraction, Ocular/physiology , Surveys and Questionnaires , Vision Tests , Visual Acuity/physiologyABSTRACT
OBJECTIVE: The development of somatoform illnesses is often associated with prior psychiatric illness and life stress. Broken heart syndrome has been associated with a range of stressors and we aimed to investigate if psychiatric illnesses are risk factors for developing broken heart syndrome. METHODS: We systematically assessed for antecedent psychiatric risk factors in two groups of cases (people who developed sporadic and earthquake-related broken heart syndrome) and compared them to a control group of healthy volunteers. RESULTS: We found that of the ten psychiatric risk factors examined, only 'neuroticism' significantly differed between participants with broken heart syndrome and healthy volunteers. CONCLUSION: There was no association between previous psychiatric illness and development of broken heart syndrome in this study. Clinical assessment of psychiatric risk factors may not identify patients at increased risk of broken heart syndrome.
