Identification of a novel splice site mutation in the DNAAF4 gene of a Chinese patient with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare hereditary orphan condition that results in variable phenotypes, including infertility. About 50 gene variants are reported in the scientific literature to cause PCD, and among them, dynein axonemal assembly factor 4 ( DNAAF4 ) has been recently reported. DNAAF4 has been implicated in the preassembly of a multiunit dynein protein essential for the normal function of locomotory cilia as well as flagella. In the current study, a single patient belonging to a Chinese family was recruited, having been diagnosed with PCD and asthenoteratozoospermia. The affected individual was a 32-year-old male from a nonconsanguineous family. He also had abnormal spine structure and spinal cord bends at angles diagnosed with scoliosis. Medical reports, laboratory results, and imaging data were investigated. Whole-exome sequencing, Sanger sequencing, immunofluorescence analysis, hematoxylin-eosin staining, and in silico functional analysis, including protein modeling and docking studies, were used. The results identified DNAAF4 disease-related variants and confirmed their pathogenicity. Genetic analysis through whole-exome sequencing identified two pathogenic biallelic variants in the affected individual. The identified variants were a hemizygous splice site c.784-1G>A and heterozygous 20.1 Kb deletion at the DNAAF4 locus, resulting in a truncated and functionless DNAAF4 protein. Immunofluorescence analysis indicated that the inner dynein arm was not present in the sperm flagellum, and sperm morphological analysis revealed small sperm with twisted and curved flagella or lacking flagella. The current study found novel biallelic variants causing PCD and asthenoteratozoospermia, extending the range of DNAAF4 pathogenic variants in PCD and associated with the etiology of asthenoteratozoospermia. These findings will improve our understanding of the etiology of PCD.

[Illness cognition and related factors in patients with prostate cancer].

OBJECTIVE: To study the illness cognition and related factors in patients with prostate cancer (PCa). METHODS: Using the convenience-sampling method, we selected 231 PCa patients treated in a general hospital in Xuzhou from October 2019 to October 2020. We conducted a cross-sectional study of the cases based on the general data of the patients and their scores on the Illness Cognition Questionnaire (ICQ). RESULTS: The PCa patients showed a high negative and a low positive illness cognition. The ICQ scores of the patients were high on "helplessness" (13.70 ± 3.54) and low on "acceptance" (16.64 ± 3.37) and "perceived benefits" (13.93 ± 3.76). Age, disease duration, disease stage and number of children were the four factors included in the regression equation of the participants' illness cognition. CONCLUSION: Negative illness cognition is high in PCa patients, higher in those at a younger age, with a longer disease duration, or with more than one child than in those at an older age, with a shorter disease duration, or with only one or no child.

[Family-centered psychological support helps improve illness cognition and quality of life in patients with advanced prostate cancer].

OBJECTIVE: To explore the effect of family-centered psychological support (FCPS) on illness cognition and quality of life in patients with advanced prostate cancer (PCa). METHODS: Using a randomized controlled study design, we divided 84 advanced PCa patients into an intervention group and a control group, all provided with PCa-related knowledge and answers to their questions, while the former group with FCPS in addition. Before, immediately after and at 1 and 3 months after intervention, we evaluated the effectiveness using the Illness Cognition Questionnaire (ICQ) and Functional Assessment of Cancer Therapy － Prostate (FACT-P). RESULTS: Totally, 78 of the patients completed the whole intervention procedure, 38 in the intervention and 40 in the control group. There were statistically significant differences between the intervention and control groups in the scores on the three factors of ICQ acceptance (17.89 ± 3.86 vs 15.20 ± 2.83, t = 3.528, P < 0.05), perceived benefits (18.68 ± 3.02 vs 17.08 ± 2.74, t = 2.465, P < 0.05) and helplessness (13.37 ± 3.00 vs 15.63 ± 3.11, t = －3.259, P < 0.05) immediately after intervention, and so were there at 1 and 3 months after intervention (P < 0.05). The patients in the intervention group showed remarkably higher quality of life scores than the controls immediately after (100.59 ± 11.66 vs 92.20 ± 9.54, t = 7.943, P < 0.05) and at 1 month (93.03 ± 13.33 vs83.55 ± 14.29, t = 3.481, P < 0.05) and 3 months after intervention (85.66 ± 17.39 vs 75.95 ± 16.66, t = 3.025, P < 0.05). The covariance analysis found that, excluding the time effect, FCPS significantly improved the positive illness cognition of the patients (P < 0.05). CONCLUSIONS: Family-centered psychological support contributes to the positive illness cognition of the patients with advanced PCa and helps improve their quality of life, and therefore deserves to be popularized in clinical practice.

[Pathological study of unexpected sudden death clustered in family or village in Yunnan province: report of 29 cases of autopsy].

OBJECTIVE: To investigate the pathological features and causes of sudden death clustered in family or village in Yunnan province so as to provide the morphological basis for exploring its etiology and medical intervention. METHODS: Autopsy was performed on 29 cases of clustered in family or village in Yunnan province during the period 1991-2006, 16 males and 13 females, aged 32 (8-69), accounting for 10.2% of whole sudden unexpected deaths occurring in the same period. The heart, lung, liver, spleen, brain, kidney, intestinal tract, and other organs were examined macroscopically and histologically, including a study of cardiac conduction system in 5 cases. Pathological diagnosis of myocarditis was based on the Dallas Criteria and World Heart Federation's consensus while the histological evaluation of Keshan disease referred the China national guideline for pathological diagnosis of Keshan disease. RESULTS: Based on the main pathological changes and the causes of death, these cases were classified into seven groups (group A-G). Group A comprised 11 cases (38%) with lymphocytic myocarditis accompanied with focal myocardial necrosis or degeneration. Group B comprised 3 cases (10%) with neutrophil myocarditis accompanied with focal myocytolysis or coagulation necrosis. Group C comprised 4 cases (14%) with arrhythmogenic right ventricle cardiomyopathy in which fatty infiltration of myocardium was the only pathological finding. Group D comprised 2 cases (7%) with ischemic heart disease in which fresh or old foci of myocardial infarction were found but coronary stenosis was shown only in one case. Group E comprised 2 cases (7%) with left ventricle hypertrophy and obstructive muscle bundle in the outflow of left ventricle. Group F comprised 2 cases (7%) with allergic bronchitis or chronic bronchitis and pulmonary emphysema. Group G comprised the remaining 5 cases (17%) without any pathological finding that could explain sudden death. No cases suffered with Keshan disease and dilated cardiomyopathy. Focal but not diffuse inflammatory infiltration was the prominent histological feature of myocarditis in Yunnan cases. Among the five cases with histological examination of cardiac conduction system, 2 cases were detected to suffer from acute hemorrhage in His bundle and its left branching site, and the atrioventricular node of 1 case was involved. Different pathological changes coexisted in 4 pairs of family members as a cluster of sudden deaths. 3 of 4 first deaths had focal myocarditis and the other one had chronic infection. But 3 secondary deaths had myocardial ischemia and the other one had arrhythmogenic right ventricle cardiomyopathy. Pulmonary edema, acute respiratory infection and congestive or ischemic liver necrosis were found in some cases simultaneously. CONCLUSION: The pathological changes of the cases of clustered sudden death in Yunnan province are various, such as myocarditis, myocardial dysplasia and the other lethal heart-lung disorders. No case of Keshan disease has been found. Arrhythmogenic right ventricle cardiomyopathy and other foundational heart diseases might act as a background. It is very hard to contribute only one etiological factor to the clustering of sudden death in Yunnan. It was most likely that multiple factors cluster and trigger an outbreak of death in a definite time and space.