To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The essence of sub-critical transition of oscillatory boundary-layer flows is the non-modal growth of finite-amplitude disturbances. The current understanding of the mechanisms of the orderly and bypass transitions of oscillatory boundary-layer flows is limited. The present study adopts optimisation approaches to predict the maximum energy amplification of two- and three-dimensional perturbations in response to the optimal initial disturbance with or without external forcing. A series of direct numerical simulations are also performed to compare with the results obtained from the stability analyses. In particular, the optimal initial perturbation similar to a Tollmien–Schlichting (T–S) wave yields the largest transient growth under the combined effects of the Orr mechanism and inflectional point instability. With a considerable level of two-dimensional disturbance, the vortex tube nonlinearly develops from the T–S-like wave, and then either deforms into a $\varLambda$-vortex in the near-wall region or rolls up to the free shear region. The further burst of turbulence can follow the first pathway as K-type transition or the second one as vortex tube breakdown due to the elliptical instability. Additionally, non-modal growth can initiate the inception of streaky structures by favourable three-dimensional initial perturbations and/or forcing. The secondary instabilities responsible for the streak breakdown are classified as the varicose (symmetric) and sinuous (anti-symmetric) modes. Under a sufficiently high level of three-dimensional disturbance, the bypass transition is predominantly characterised by the formation of the sinuous mode and turbulent spots, which leads to the suppression of inflection point instability.
Increasing evidence supports sarcopenia as an important parameter for predicting cardiometabolic risks. The objective of this study was to investigate the relationship between muscle mass, muscle strength, and physical performance, and cardiovascular risk among older community-dwelling adults.
The associations between dynapenia, sarcopenia, and Framingham risk score (FRS) were estimated by multivariate regression models.
Muscle mass is estimated by skeletal muscle mass index using a bioelectrical impedance analysis. Muscle strength is measured by handgrip strength using an analogue isometric dynamometer. Physical performance is measured by gait speed using a 6-m walking distance. Dynapenia was defined as low muscle strength and/or slow gait speed presents with normal muscle mass. The diagnosis of presarcopenia and sarcopenia was based on criteria proposed by the Asian Working Group for Sarcopenia in 2014. The FRS was used for evaluating 10-year coronary heart disease (CHD) risk.
Adults aged 65 years and older who attended health examinations from 2015 to 2017 were recruited.
There were totally 709 subjects enrolled in this study. Dynapenic men (n 47) had 17·70 ± 5·08 % FRS and sarcopenic women (n 74) had 7·74 ± 6·06 % FRS. Participants with presarcopenia had the lowest FRS (men: 15·41 ± 5·35 %; women: 5·25 ± 3·70 %). Men with dynapenia had higher FRS than the presarcopenia group with odds ratio (OR) of 2·52 (95 % confidence interval (CI): 1·03, 6·14). Women with sarcopenia had significantly higher FRS than the presarcopenia group with OR of 2·81 (95 % CI: 1·09, 7·27).
Older dynapenic men and older sarcopenic women had higher risks of 10-year CHD. Presarcopenic older adults had the lowest CHD risk in both genders.
For individual cultures, findings on regulating embryo density by changing the microdrop volume are contradictory. The aim of this study was to investigate the relationship between embryo density and the developmental outcome of day 3 embryos after adjusting covariates. In total, 1196 embryos from 206 couples who had undergone in vitro fertilization treatment were analyzed retrospectively. Three embryo densities were used routinely, i.e. one embryo in a drop (30 μl/embryo), two embryos in a drop (15 μl/embryo) and three embryos in a drop (10 μl/embryo). Embryo quality on day 3 was evaluated, both the cell number of day 3 embryos and the proportion of successful implantations served as endpoints. Maternal age, paternal age, antral follicles and level of anti-Müllerian hormone, type of infertility, controlled ovarian stimulation protocol, length of stimulation, number of retrieved oocytes, number of zygotes (two pronuclei) and insemination type were covariates and adjusted. After adjusting fully for all covariates, the cell number of day 3 embryos was significantly increased by 0.40 (95% CI 0.00, 0.79; P = 0.048) and 0.78 (95% CI 0.02, 1.54; P = 0.044) in the 15 μl/embryo and 10 μl/embryo group separately, compared with the 30 μl/embryo group. The proportions of implanted embryos were 42.1%, 48.7% and 0.0% in the 30 μl/embryo, 15 μl/embryo and 10 μl/embryo groups respectively. There was no statistical significance (P = 0.22) between the 30 μl/embryo group and the 15 μl/embryo group. After adjusting for confounders that were significant in univariate analysis, embryo density was still not associated with day 3 embryo implantation potential (P > 0.05). In a 30-μl microdrop, culturing embryos with an embryo density of both 15 and 10 μl/embryo increased the cell number of day 3 embryos, which did not benefit embryo implanting potential, compared with individual culture of 30 μl/embryo.
Accumulating evidence suggests that supplementation of omega-3 polyunsaturated fatty acids (ω−3 PUFAs) was associated with reduction in risk of major cardiovascular events. This meta-analysis was to systematically evaluate whether daily supplementation and accumulated intake of ω−3 PUFAs is associated with improved left ventricular (LV) remodeling in patients with chronic heart failure (CHF). Articles were obtained from Pubmed, Clinical key and Web of Science from inception to January 1 in 2021, and a total of 12 trials involving 2162 participants were eligible for inclusion. The sources of study heterogeneity were explained by I2 statistic and subgroup analysis. Compared with placebo groups, ω−3 PUFAs supplementation improved LV ejection fraction (LVEF) (11 trials, 2112 participants, WMD=2.52, 95%CI 1.25 to 3.80, I2=87.8%) and decreased LV end-systolic volume (LVESV) (5 studies, 905 participants, WMD=−3.22, 95%CI −3.67 to −2.77, I2=0.0%) by using the continuous variables analysis. Notably, the high accumulated ω−3 PUFAs dosage groups (≥600g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤300g and 300-600g) showed no effects on LVEF. In addition, ω−3 PUFAs supplementation decreased the levels of pro-inflammatory mediators including tumor necrosis factor−α (TNF-α), interleukin-6 (IL-6) and hypersensitive-c-reactive protein (Hs-CRP). Therefore, the present meta-analysis demonstrated that ω−3 PUFAs consumption was associated with a substantial improvement of LV function and remodeling in patients subjected to CHF. The accumulated dosage of ω-3 PUFAs intake is vital for its cardiac protective role.
The Lochkovian (Lower Devonian) conodont biostratigraphy in China is poorly known, and conodont-based subdivision schemes for the Lochkovian in peri-Gondwana (the Spanish Central Pyrenees, the Prague Synform, Sardinia, and the Carnic Alps) have not been tested in China. Therefore, we studied conodonts from the lower part (Bed 9 to Bed 13) of the Shanjiang Formation at the Alengchu section of Lijiang, western Yunnan to test the application of established subdivision schemes. The conodont fauna is assignable to 12 taxa belonging to eight genera (Ancyrodelloides, Flajsella, Lanea, Wurmiella, Zieglerodina, Caudicriodus, Pelekysgnathus, and Pseudooneotodus), and enables recognition of two chronostratigraphical intervals from the lower part of the Shanjiang Formation. The interval ranging from the uppermost part of Bed 9 to the upper part of Bed 10 belongs to the lower Lochkovian; whereas an interval covering the uppermost part of Bed 11 to the upper part of Bed 13 is correlated with the upper half of the middle Lochkovian. The Silurian-Devonian boundary is probably located within Bed 9, in the basal part of the Shanjiang Formation. However, the scarcity of specimens precludes definitive identification of bases of the lower, middle, and upper Lochkovian as well as other conodont zones recognized in peri-Gondwana.
The sudden outbreak of the COVID-19 pandemic has caused tremendous challenges to the medical system. The government and hospitals have taken robust measures to curb the spread of the deadly virus. Its impact on routine medical services is gradually being taken seriously.
To identify the impact of the novel Coronavirus pandemic on emergency department (ED) patient flow and the performance of the routine ED service.
This retrospective cohort study was undertaken in a tertiary public teaching hospital ED in Chengdu, China. ED data of patients were routinely collected to compare demographic, clinical characteristics and outcomes during an 8-week period from January 1, 2019 to February 25, 2020. Data were analyzed with the chi-square statistical test.
Over the study periods, there were 31855 and 25244 patients presented to the ED in 2019 and 2020 respectively. During the pandemic period in 2020, the daily number of average ED visits was lower than that in 2019 (430 ± 134.9 versus 572 ± 38.6, P = 0.00), with fewer triage 1&2 cases (145 ± 33.3 versus 178 ± 15.0, P = 0.00). Nevertheless, the mortality increased remarkably during the pandemic period in 2020 (0.2% versus 0.1%, P = 0.009), with higher APACHE II scores (28 versus 19, P = 0.022) and shorter ED elapsed time (0.2 versus 1.4 days, P = 0.016) among these death cases.
The COVID-19 pandemic had an evident impact on the patient’s behavioral patterns and routine emergency services, which caused higher ED mortality.
The most important issue for the clinical application of sarcopenic obesity (SO) is the lack of a consensus definition. The aim of the present study was to determine the best measurement for SO by estimating the association between various definitions and the risk of falls and metabolic syndrome (MS). We studied a community of 765 adults aged 65 years and older in 2015–2017. Sarcopenia obesity was measured by sarcopenia (defined by low muscle mass with either low handgrip strength or low gait speed or both) plus obesity (defined by waist circumference, body fat percentage and BMI). The MS was defined according to the National Cholesterol Education Program ATP III. Logistic regression models were constructed to examine the relationships between sarcopenia obesity and risk of fall and MS. In the analysis of the fall risk with SO defined by waist circumference, the participants with non-sarcopenia/non-obesity were treated as the reference group. The OR to fall in participants with SO was 10·16 (95 % CI 2·71, 38·13) after adjusting for confounding covariates. In the analysis of the risk of the MS between participants with individual components of sarcopenia coupled with obesity defined by waist circumference, the risk was statistically significant for low gait speed (OR: 7·19; 95 % CI 3·61, 14·30) and low grip strength (OR: 9·19; 95 % CI 5·00, 16·91). A combination of low grip strength and abdominal obesity for identifying SO may be a more precise and practical method for predicting target populations with unfavourable health risks, such as falls risk and MS.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating “气血” (“Qi-Xue”, i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that “meridians are the conduit for Qi-Xue circulation” in CTM.
The present study investigated the association between fibre degradation and the concentration of dissolved molecular hydrogen (H2) in the rumen. Napier grass (NG) silage and corn stover (CS) silage were compared as forages with contrasting structures and degradation patterns. In the first experiment, CS silage had greater 48-h DM, neutral-detergent fibre (NDF) and acid-detergent fibre degradation, and total gas and methane (CH4) volumes, and lower 48-h H2 volume than NG silage in 48-h in vitro incubations. In the second experiment, twenty-four growing beef bulls were fed diets including 55 % (DM basis) NG or CS silages. Bulls fed the CS diet had greater DM intake (DMI), average daily gain, total-tract digestibility of OM and NDF, ruminal dissolved methane (dCH4) concentration and gene copies of protozoa, methanogens, Ruminococcus albus and R. flavefaciens, and had lower ruminal dH2 concentration, and molar proportions of valerate and isovalerate, in comparison with those fed the NG diet. There was a negative correlation between dH2 concentration and NDF digestibility in bulls fed the CS diet, and a lack of relationship between dH2 concentration and NDF digestibility with the NG diet. In summary, the fibre of CS silage was more easily degraded by rumen microorganisms than that of NG silage. Increased dCH4 concentration with the CS diet presumably led to the decreased ruminal dH2 concentration, which may be helpful for fibre degradation and growth of fibrolytic micro-organisms in the rumen.
Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.
The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.
We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).
Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.
Telocytes (TCs) are very long, non-neuronal, somatic cells whose function is widely believed to be involved in providing connections between different cells within the body. The cellular characteristics of TCs in various organs have been studied by immunohistochemistry, double immunofluorescence and electron microscopy in different vertebrate species, and here we investigate the proposed properties of these cells in the context of the “meridian” in Chinese Traditional Medicine (CTM). The results show that TCs and their long extensions, telopodes (Tps) develop a complicated network by homo- and heterocellular junctions in the connective tissue throughout the body, which can connect the skin with distant organs. In concept, this is the analogue of ancient meridian maps connecting skin acupoints with the viscera. Various active cells and extracellular vesicles including exosomes move along Tps, which, along with developed mitochondria within the podoms of Tps, may account for the structural evidence for “Qi” (vital energy and signal communication) in CTM. Morphological associations of TCs with the nerve, vascular, endocrine, and immune systems are also compatible with previously proposed meridian theories in CTM. Close relationships exist between TCs and collagen fiber bundles and some structures in skin fascia provide the microanatomical support for acupuncture treatment based on the meridian principle. The dynamicity in the distribution and structure of TCs reflects the plasticity of the meridian at the cellular level. As the same attribute, both the meridian and the TC have been associated with various diseases. Here, we summarize structural analogues between the TC and the meridian, suggesting that TCs have the cytological characteristics of the CTM meridian. We, therefore, hypothesize that TCs are the “essence cells” of the CTM meridian, which can connect and integrate different cells and structures in the connective tissue.
There has been considerable interest in stratospheric airships as a cost-effective alternative to earth orbit satellites for sightseeing, aerial photography, communication and carrying weapons, etc. Many countries have plans to develop the airship owing to its greatly expected usage. The suspended curtain plays a vital role in force transmission in stratospheric airships but lacks attention. In this paper, the relationship between the optimal shape of suspended curtain and load conditions was studied through CAE Abaqus and Isight. Firstly, by using secondary development function of Abaqus, parametric FEA models of suspended curtains and envelopes have been established, several parameters were used to describe the shape of suspended curtains. Secondly, parameters of the suspended curtain shape were optimized under different loading conditions by means of the genetic algorithm. Lastly, through the analysis of the results, some conclusions are summarized: The relationship between n1(n2) and nb was found to be linear when the suspended curtain is subjected to vertical load. The stress transfer law of suspended curtain and inflatable membrane structure under the inclined load were also obtained, which are valuable for the structural engineering design of stratospheric airships..
Psychiatric disorders are a group of complex psychological syndromes with high prevalence. Recent studies observed associations between altered plasma proteins and psychiatric disorders. This study aims to systematically explore the potential genetic relationships between five major psychiatric disorders and more than 3,000 plasma proteins.
The genome-wide association study (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) were driven from the Psychiatric GWAS Consortium. The GWAS datasets of 3,283 human plasma proteins were derived from recently published study, including 3,301 study subjects. Linkage disequilibrium score (LDSC) regression analysis were conducted to evaluate the genetic correlations between psychiatric disorders and each of the 3,283 plasma proteins.
LDSC observed several genetic correlations between plasma proteins and psychiatric disorders, such as ADHD and lysosomal Pro-X carboxypeptidase (p value = 0.015), ASD and extracellular superoxide dismutase (Cu-Zn; p value = 0.023), BD and alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (p value = 0.007), MDD and trefoil factor 1 (p value = 0.011), and SCZ and insulin-like growth factor-binding protein 6 (p value = 0.011). Additionally, we detected four common plasma proteins showing correlation evidence with both BD and SCZ, such as tumor necrosis factor receptor superfamily member 1B (p value = 0.012 for BD, p value = 0.011 for SCZ).
This study provided an atlas of genetic correlations between psychiatric disorders and plasma proteome, providing novel clues for pathogenetic and biomarkers, therapeutic studies of psychiatric disorders.
Chlamydia spp. are a group of obligate intracellular pathogens causing a number of diseases in animals and humans. Avian chlamydiosis (AC), caused by Chlamydia psittaci (C. psittaci) as well as new emerging C. avium, C. gallinacea and C. ibidis, have been described in nearly 500 avian species worldwidely. The Crested Ibis (Nipponia nippon) is a world endangered avian species with limited population and vulnerable for various infections. To get a better understanding of the prevalence of Chlamydia spp. in the endangered Crested Ibis, faecal samples were collected and analysed. The results confirmed that 20.20% (20/99) of the faecal samples were positive for Chlamydiaceae and were identified as C. ibidis with co-existence of C. psittaci in one of the 20 positive samples. In addition, ompA sequence of C. psittaci obtained in this study was classified into the provisional genotype Matt116, while that of C. ibidis showed high genetic diversity, sharing only 77% identity with C. ibidis reference strain 10-1398/6. We report for the first time the presence of C. ibidis and C. psittaci in the Crested Ibis, which may indicate a potential threat to the endangered birds and should be aware of the future protection practice.
Severe phase coarsening and separation in Sn–Bi alloys have brought increasing reliability concern in microelectronic packages. In this study, a phase field model is developed to simulate the microstructural evolution and evaluate the change in macroscopic physical properties of the flip chip Cu/Sn58Bi/Cu joint under the conditions of isothermal aging, as well as the coupled loads of elastic stress and electric current stressing. Results show that large-sized Bi-rich phase particles grow up at the expense of small-sized ones. Under the coupled loads, Bi atoms migrate along the electron flow direction, consequently Bi-rich phase segregates to form a Bi-rich phase layer at the anode. The current crowding ratio in the solder decreases rapidly first and then fluctuates slightly with time. Current density and von Mises stress exhibit inhomogeneous distribution, and both of them are higher in the Sn-rich phase than in the Bi-rich phase. Electric current transfers through the Sn-rich phase and detours the Bi-rich phase. As time proceeds, the resistance of the solder joint increases, and the average von Mises stress of the solder joint decreases. The Bi-rich phase coarsens much faster under the coupled loads than under the conditions of isothermal aging.
In order to reveal the quantitative relationship between fatigue crack deflection path and cross-sectional grain boundary (GB) arrangement of metallic nanolayered composites (NLCs), a stochastic model was established based on the interface-dominant fatigue damage for the ultrafine-scale NLCs. The model indicates that the crack deflection length decreases with decreasing GB arrangement deviation and grain size of constituent layers. The observation and quantitative analysis of fatigue cracking behavior of the Cu/W multilayers with a layer thickness of 5 and 20 nm was conducted to verify the model.
Fatigue performance of metallic nanolayered composites (NLCs) has been gaining more and more attention due to the rapid development in the field of both micro-electro-mechanical systems and high-performance engineering structure materials and the increasing demand for long-term fatigue reliability. Metallic NLCs have exhibited different damage behaviors due to the effect of high-density heterogeneous interface compared with bulk materials and thin metal films. In this review paper, the cyclic deformation damage behavior, fatigue cracking feature, and fatigue properties of some metallic NLCs are reviewed. Effects of length scales, including layer thickness and grain size, on fatigue damage behaviors of the NLCs are revealed, and the transition of the fatigue cracking behavior and the corresponding damage mechanism are discussed. Then, the fatigue properties of some typical metallic NLCs are presented and compared with that of bulk materials and metal thin films. The effect of interface type and grain boundary alignment is also discussed to correlate with fatigue cracking resistance of the NLCs. Finally, some prospective research topics on fatigue performance of metallic NLCs are addressed.
The present study used a person-centered approach to identify math motivation profiles under self-determination theory, and examine whether math achievement varies across different profiles. Data were collected from 2,137 children. Five student motivation profiles were identified: a “high quality” profile characterized by high levels of intrinsic and identiﬁed motivation and a low level of controlled motivation, a “high quantity” profile characterized by high levels of these three kinds of motivation, a “low quantity” profile characterized by low levels of these three kinds of motivation, a “poor quality” profile characterized by a high level of controlled motivation and low levels of intrinsic and identiﬁed motivation, and a “low autonomous motivation” profile characterized by very low levels of intrinsic and identiﬁed motivation. These five profiles differed in math achievement. We found that students in the high quality profile had the highest level of math achievement compared to those in the other profiles. This result indicated that the quality of motivation was more important than the amount of motivation.
Dilated Cardiomyopathy is a serious heart disorder that may induce sudden cardiac death and heart failure. Significant progress has been made in understanding the molecular basis of dilated cardiomyopathy. In previous studies, mutations in more than fifty genes have been identified in dilated cardiomyopathy patients. The purpose of this study was to detect the genetic lesion in a family from the central south of China affected by severe dilated cardiomyopathy.
Whole-exome sequencing combined with cardiomyopathy-related genes list were used to analyse the mutations of the proband. Co-segregation analysis was performed by Sanger sequencing.
Results and conclusions
Two novel heterozygous mutations – Myosin Binding Protein C: p.L1014RfsX6 and Titin: p.R9793X – were identified in the proband. The deletion mutation c.3041delT/p.L1014RfsX6 caused a premature stop codon at position 1020 in exon 28 of the Myosin Binding Protein C. The nonsense mutation, c.29377 C>T/ p. R9793X, of Titin was located in the highly evolutionarily conserved domain, resulting in truncation of the Titin protein as well. Co-segregation analysis further revealed that the Myosin Binding Protein C mutation came from his mother and the Titin mutation came from his father. Both mutations are reported in dilated cardiomyopathy patients for the first time. Our study not only provides a unique example of the genes and molecular mechanisms involved in dilated cardiomyopathy but also expands the spectrum of Myosin Binding Protein C and Titin mutations and contributes to the genetic diagnosis and counselling of dilated cardiomyopathy patients.