Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

[Pharmacological therapies for height improvement in pubertal children with short stature]. / 青春期矮身材儿童身高改善的药物治疗.

Short stature in puberty significantly affects the physical and mental health of adolescents. The continuous acceleration of skeletal maturation, caused by sex hormones during puberty, limits the time available for growth and poses a considerable challenge for the treatment of short stature. To date, there is still no standardized treatment protocol for this disorder. However, puberty is the last period to improve the final adult height. Currently, commonly used pharmacological treatments in clinical settings include recombinant human growth hormone, gonadotropin-releasing hormone analogs, and third-generation aromatase inhibitors. In recent years, personalized treatment aiming to improve the final adult height has become a key focus in clinical practice. This article provides a comprehensive summary of research on pharmacological therapies for height improvement in pubertal children with short stature, offering valuable insights for healthcare professionals.

Complete genome sequence of Bacillus halotolerans F29-3, a fengycin-producing strain.

Bacillus halotolerans F29-3, a Gram-positive bacterium, is recognized for its synthesis of the antifungal substance fengycin. This announcement introduces the complete genome sequence and provides insights into the genetic products related to antibiotic secondary metabolites, including non-ribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and NRPS/PKS combination.

Cellular localization and potential ligands of a novel scavenger receptor class B/CD36 protein homolog (Pt-SRB2) identified in the marine crab, Portunustrituberculatus.

The scavenger receptor class B family proteins (SRB) are multiligand membrane receptor proteins. Herein, a novel SRB homolog (Pt-SRB2) was identified in Portunus trituberculatus. The open reading frame of Pt-SRB2 was predicted to encode 520 amino acid residues comprising a typical CD36 domain. Phylogenetic analysis showed that Pt-SRB2 distinctly clustered with the SRB homologs of most crustaceans and Drosophila but was separate from all vertebrate CD36/SRB. Semi-quantitative and Real-time quantitative PCR revealed that the abundance of Pt-SRB2 transcripts was the highest in hepatopancreas than in other tested tissues. Overexpressed Pt-SRB2 was distributed primarily in the cell membrane and cytoplasm of HEK293T or Drosophila Schneider 2 cells. In crab hemocytes, Pt-SRB2 was distributed primarily in the cell membrane by immunofluorescence staining. In addition, the immunofluorescence staining showed that green fluorescence signals were mainly located in the inner lumen membrane of the hepatopancreatic tubules. Moreover, solid-phase enzyme-linked immunosorbent assay revealed that rPt-SRB2-L exhibited relative high affinity with lipopolysaccharides, and relative moderate binding affinity with lipoteichoic acid or peptidoglycan. Of note, rPt-SRB2-L showed high binding affinity with eicosapentaenoic acid among a series of long-chain polyunsaturated fatty acids. Taken together, this study provided valuable data for understanding the functions of the crab CD36/SRB.

Molecular characterization and functional analysis of TRIM37 from black tiger shrimp (Penaeus monodon).

The family of TRIM proteins with E3 ubiquitin ligase activity served important roles in the regulation of innate immune processes, in particular antiviral and proinflammatory cytokine responses. In this study, a novel TRIM37 homolog was identified from Penaeus monodon (named PmTRIM37). The PmTRIM37 protein contained three conserved domains (one RING finger domain, a B-box, and one Coiled-coil region) at its N-terminal and one Meprin and MATH domain at its C-terminal. The MATH domain was the characteristic of TRIM37 family. PmTRIM37 has relatively high expression in immune-related tissues such as hepatopancreas, gills, lymphoid organs and hemocytes. The expression levels of PmTRIM37 in hepatopancreas and lymphoid organs were significantly up-regulated after white spot syndrome virus (WSSV) infection. Knock down of PmTRIM37 promoted WSSV replication and VP28 expression, suggesting that PmTRIM37 played a negative role in WSSV infection. Further studies revealed that PmTRIM37 positively regulated the NF-κB pathway and Antimicrobial peptides (AMP) expression during WSSV infection. These findings indicated that PmTRIM37 might restrict WSSV replication by positively regulating NF-κB pathway during WSSV infection in P. monodon.

Rise and metabolic roles of Vibrio during the fermentation of crab paste.

Microbial community may systematically promote the development of fermentation process of foods. Traditional fermentation is a spontaneous natural process that determines a unique nutritional characteristic of crab paste of Portunus trituberculatus, However, rare information is available regarding the development pattern and metabolic role of bacterial community during the fermentation of crab paste. Here, using a 16S rRNA gene amplicon sequencing technology, we investigated dynamics of bacterial community and its relationship with metabolites during the fermentation of crab paste. The results showed that bacterial community changed dynamically with the fermentation of crab paste which highlighted by consistently decreased α-diversity and overwhelming dominance of Vibrio at the later days of fermentation. Vibrio had a positive correlation with trimethylamine, hypoxanthine, formate, and alanine while a negative correlation with inosine and adenosine diphosphate. In contrast, most of other bacterial indicators had a reverse correlation with these metabolites. Moreover, Vibrio presented an improved function potential in the formation of the significantly increased metabolites. These findings demonstrate that the inexorable rise of Vibrio not only drives the indicator OTUs turnover in the bacterial community but also has incriminated the quality of crab paste from fresh to perished.

Early detection of myocardial ischemia in resting ECG: analysis by HHT.

BACKGROUND: Exercise electrocardiography (ECG) is a noninvasive test aiming at producing ischemic changes. However, resting ECG cannot be adopted in diagnosing myocardial ischemia till ST-segment depressions. Therefore, this study aimed to detect myocardial energy defects in resting ECG using the Hilbert-Huang transformation (HHT) in patients with angina pectoris. METHODS: Electrocardiographic recordings of positive exercise ECG by performing coronary imaging test (n = 26) and negative exercise ECG (n = 47) were collected. Based on the coronary stenoses severity, patients were divided into three categories: normal, < 50%, and ≥ 50%. During the resting phase of the exercise ECG, all 10-s ECG signals are decomposed by HHT. The RT intensity index, composed of the power spectral density of the P, QRS, and T components, is used to estimate the myocardial energy defect. RESULTS: After analyzing the resting ECG using HHT, the RT intensity index was significantly higher in patients with positive exercise ECG (27.96%) than in those with negative exercise ECG (22.30%) (p < 0.001). In patients with positive exercise ECG, the RT intensity index was gradually increasing with the severity of coronary stenoses: 25.25% (normal, n = 4), 27.14% (stenoses < 50%, n = 14), and 30.75% (stenoses ≥ 50%, n = 8). The RT intensity index of different coronary stenoses was significantly higher in patients with negative exercise ECG, except for the normal coronary imaging test. CONCLUSIONS: Patients with coronary stenoses had a higher RT index at the resting stage of exercise ECG. Resting ECG analyzed using HHT could be a method for the early detection of myocardial ischemia.

Congenital biliary atresia caused by GPC1 gene mutation in Chinese siblings: A case report.

BACKGROUND: Congenital biliary atresia (CBA) is a serious hepatobiliary disease in children with unknown etiology. Its outcome is often liver transplantation or death. Clarifying the etiology of CBA is of great significance for prognosis, treatment, and genetic counseling. CASE SUMMARY: A male Chinese infant at an age of 6 mo and 24 d was hospitalized because of "yellow skin for more than 6 mo". Soon after birth, the patient developed jaundice, which then progressively intensified. A "laparoscopic exploration" indicated "biliary atresia". After coming to our hospital, genetic testing suggested a GPC1 mutation [loss 1 (exons 6-7)]. The patient recovered and was discharged after living donor liver transplantation. After discharge, the patient was followed up. The condition was controlled by oral drugs, and the patient's condition was stable. CONCLUSION: CBA is a complex disease with a complex etiology. Clarifying the etiology is of great clinical importance for treatment and prognosis. This case reports CBA caused by a GPC1 mutation, which enriches the genetic etiology of biliary atresia. However, its specific mechanism needs to be confirmed by further research.

The Functions of Pt-DIC and Pt-Lamin B in Spermatogenesis of Portunus trituberculatus.

Cytoplasmic Dynein is a multiple-subunit macromolecular motor protein involved in the transport process of cells. The Dynein intermediate chain (DIC) is one of the subunits of Dynein-1. In our previous studies, we showed that Pt-DIC may play an important role in the nuclear deformation of spermiogenesis in Portunus trituberculatus. Lamin B is essential for maintaining nuclear structure and functions. Surprisingly, Pt-Lamin B was expressed not only in the perinucleus but also in the pro-acrosome during spermiogenesis in P. trituberculatus. Studies have also shown that Dynein-1 can mediate the transport of Lamin B in mammals. Thus, to study the relationship of Pt-DIC and Pt-Lamin B in the spermatogenesis of P. trituberculatus, we knocked down the Pt-DIC gene in P. trituberculatus by RNAi. The results showed that the distribution of Pt-DIC and Pt-Lamin B in spermiogenesis was abnormal, and the colocalization was weakened. Moreover, we verified the interaction of Pt-DIC and Pt-Lamin B via coimmunoprecipitation. Therefore, our results suggested that both Pt-DIC and Pt-Lamin B were involved in the spermatogenesis of P. trituberculatus, and one of the functions of Dynein-1 is to mediate the transport of Lamin B in the spermiogenesis of P. trituberculatus.

Leaf chlorophyll parameters and photosynthetic characteristic variations with stand age in a typical desert species (Haloxylon ammodendron).

As a desert shrub, Haloxylon ammodendron combines ecological, economic, and social benefits and plays an important role in the ecological conservation of arid desert areas. Understanding its physiological characteristics and its mechanism of light energy utilization is important for the conservation and utilization of H. ammodendron. Therefore, we selected five stands (5-, 11-, 22-, 34-, and 46-year-old) of H. ammodendron as research objects in the study and measured their photosynthetic light response curves by a portable open photosynthesis system (Li-6400) with a red-blue light source (6400-02B). Then, we measured the leaf chlorophyll parameters in the laboratory, calculated the photosynthetic characteristics by using Ye Zipiao's photosynthetic model, analyzed their variation patterns across stand ages, and explored the relationships between leaf chlorophyll parameters and photosynthetic characteristics. The results showed that leaf chlorophyll parameters and photosynthetic characteristics of H. ammodendron at different stand ages were significantly different. Chl content, P nmax, and LUEmax of H. ammodendron were V-shaped with the increase of stand age. The 5-year-old H. ammodendron was in the rapid growth period, synthesized more Chl a+b content (8.47 mg g-1) only by using a narrower range of light, and the Pnmax and LUEmax were the highest with values of 36.21 µmol m-2 s-1 and 0.0344, respectively. For the 22-year-old H. ammodendron, due to environmental stress, the values of Chl a+b content, P nmax, and LUEmax were the smallest and were 2.64 mg g-1, 25.73 µmol m-2 s-1, and 0.0264, respectively. For the older H. ammodendron, its Chl content, P nmax, and LUEmax were not significantly different and tended to stabilize but were slightly higher than those of the middle-aged H. ammodendron. On the other hand, the other photosynthetic parameters did not show significant variation patterns with stand age, such as R d, AQE, LSP, LCP, and I L-sat. In addition, we found that the relationships between Chl a+b content and P nmax and between Chl a+b content and LUEmax were highly correlated, except for the older H. ammodendron. Thus, using leaf chlorophyll content as a proxy for photosynthetic capacity and light use efficiency should be considered with caution. This work will provide a scientific reference for the sustainable management of desert ecosystems and vegetation restoration in sandy areas.

Growth hormone ameliorates hepatopulmonary syndrome and nonalcoholic steatohepatitis secondary to hypopituitarism in a child: A case report.

BACKGROUND: Craniopharyngioma is a benign tumor that usually develops in children; however, it is located in the center and close to sensitive structures, such as the pituitary gland and hypothalamus. As the hypothalamus plays a crucial role in the homeostasis of anterior pituitary hormone synthesis, damage to the hypothalamus leads to multiple pituitary hormone deficiencies and non-alcoholic fatty liver disease, including hepatopulmonary syndrome (HPS). HPS has limited treatment and poor prognosis. CASE SUMMARY: A girl aged 13 years and 6 mo underwent surgery for craniopharyngioma 6 years prior. Right craniotomy was performed with total resection via the corpus callosum approach, and the tumor at the base was approximately 3.5 cm × 3.5 cm × 4.0 cm. At 1 year postoperatively, she exhibited abdominal distension and weakness, and the laboratory tests revealed fatty liver disease. Thereafter, she had not visited the outpatient clinic for 2 years. Two years ago, she developed decreased activity endurance, severe cyanosis, chest tightness, wheezing, and intermittent and recurrent low fever after mild physical labor. Hepatobiliary ultrasonography, liver biopsy, and contrast echocardiography of the right heart showed cirrhosis and multiple pituitary hormone deficiencies, indicating HPS. After 1 year of treatment with recombinant human growth hormone, the liver function and oxygenation improved; she did not undergo liver transplantation. CONCLUSION: Craniopharyngioma surgery can easily cause hypopituitarism, which can lead to nonalcoholic steatohepatitis and HPS in children. Early growth hormone therapy is important to improve the prognosis of these diseases.

Clinical Incidence and Characteristics of Newly Diagnosed Type 1 Diabetes in Chinese Children and Adolescents: A Nationwide Registry Study of 34 Medical Centers.

Objective: To investigate the clinical incidence and characteristics of type 1 diabetes mellitus (T1DM) of children and adolescents at the time of initial diagnosis in China. Methods: Data on all pediatric patients with newly diagnosed T1DM were retrospectively collected from 34 medical centers in 25 major cities in China from January 2015 to January 2020. Patients were classified into three age groups: <5 years, 5 to <10 years, and ≥10 years of age. The same patient population was also categorized into diabetic ketoacidosis (DKA) and non-DKA groups based on clinical criteria. Results: The mean annual clinical incidence of T1DM was 3.16/100,000 from the years 2015 to 2019. A total of 6,544 patients with newly diagnosed T1DM aged 0-16 years (median 7.84 ± 3.8) were studied [ages <5 years (29.3%), 5 to <10 years (38.7%), and ≥10 years (32%)], 52.4% of them were women. In total, 90.5% of the cases were occurred in individuals without a family history. Patients had lower C-peptide (CP) and body mass index (BMI) z scores when compared with healthy children, 41.8% of them had measurable T1DM-related antibodies and 52.7% had DKA. Among all three age groups, the <5 years group had the lowest BMI z score, CP, and glycated hemoglobin (HbA1c) on average, while it had the highest incidence rate of DKA (56.9%). Compared to the non-DKA group, the DKA group was significantly younger, with a lower BMI z score and CP, higher antibody positive rate, HbA1c, and the rate of insulin pump therapy. Conclusion: The clinical incidence of T1DM in children and adolescents in China was 3.16/100,000. Patients with DKA at the first diagnosis of T1DM have a worse ß-cell function. Public health measures for the prevention and treatment of T1DM should focus on preschoolers (aged <5 years) in particular, considering the severity and the highest frequency of DKA in this age group. More efforts should be dedicated to early screening and diagnosis of the T1DM.

Treatment and five-year follow-up of type A insulin resistance syndrome: A case report.

BACKGROUND: Type A insulin resistance syndrome (TAIRS) is a rare disorder characterized by severe insulin resistance due to defects in insulin receptor signaling. No specific drugs are available for the treatment of TAIRS. We report a case of TAIRS successfully treated with pioglitazone and flutamide for 5 years. CASE SUMMARY: We present the rare case of a female patient aged 11 years and 9 mo with type A insulin resistance and an INSR heterozygous mutation (c.3614C>T), who was treated with a combination of pioglitazone and flutamide. This treatment regimen reduced hemoglobin A1c, fasting insulin and androgen levels. CONCLUSION: Pioglitazone attenuated insulin resistance in this patient with TAIRS, and flutamide ameliorated masculinization.

ATP catabolism and bacterial succession in postmortem tissues of mud crab (Scylla paramamosain) and their roles in freshness.

The seafood microbiome is highly diverse and plays an essential role in the spoilage of seafood. Nevertheless, how such a diverse microbiome influences freshness of mud crab (Scylla paramamosain) remains unclear. Here we investigated the postmortem ATP catabolism and succession of the bacterial community in the hepatopancreas and muscle of S. paramamosain using a high-performance liquid chromatography method and 16S rRNA gene amplicon sequencing. Our results showed a tissue-dependent change in ATP catabolism determinized the differences in the changes of nucleotide freshness indices of hepatopancreas and muscle over postmortem time of mud crab. The muscle K value could be used as an optimal nucleotide freshness indicator for the freshness of mud crab, with a proposed threshold of 20%. From a microbiota perspective, a more significant bacterial community change was observed in the muscle than in the hepatopancreas. These changes could result in a close relationship between ATP and its catabolites and microbial taxa in the muscle. Moreover, Photobacterium, Peptostreptococcaceae, average path distance, OTU richness, and Shannon index of muscle bacterial community markedly contributed to K value. These findings suggest that the mud crab of 4 h postmortem at room temperature is still edible. Notably, the importance of microbial community composition and interaction for the spoilage of mud crab should be carefully considered.

Rare mutation in MKRN3 in two twin sisters with central precocious puberty: Two case reports.

BACKGROUND: Caused by premature activation of the hypothalamic-pituitary-gonadal axis, there is increasing incidence of central precocious puberty (CPP), especially in girls. Makorin ring finger protein 3 (MKRN3), a maternal imprinted gene with a highly conserved sequence, is the most common genetic etiology associated with CPP. Approximately 50 different mutations in MKRN3 have been found in CPP. CASE SUMMARY: This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years. The left hand bone age of both patients revealed advanced age (9 years). Pelvic B ultrasound indicated enlargement of the ovaries. Luteinizing hormone (LH) releasing hormone testing confirmed CPP. Whole-exome sequencing detected the c.841C>T mutation in MKRN3, leading to a single base substitution, in the twins. This mutation was inherited from the father and paternal grandmother. After 3 mo of treatment with a gonadotropin-releasing hormone analog, levels of LH, follicle-stimulating hormone, and estradiol in the proband's sister returned to normal levels. CONCLUSION: Here, we report a rare mutation (c.841C>T) in MKRN3 in identical twin sisters with CPP.

Complete androgen insensitivity syndrome caused by the c.2678C>T mutation in the androgen receptor gene: A case report.

BACKGROUND: Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene (AR). However, the underlying molecular mechanisms for the majority of AR variants remain unclear. In this study, we identified a point variant in three patients with complete androgen insensitivity syndrome (CAIS), summarized the correlation analysis, and performed a literature review. CASE SUMMARY: The proband was raised as a girl. In infancy, she was first referred to hospital with a right inguinal hernia. Ultrasonography revealed the absence of a uterus and ovaries, and a testis-like structure located at the inguinal canal. Further diagnostic workup detected a 46, XY karyotype, and fluorescence in situ hybridization analysis showed the presence of the SRY gene. Histological analysis revealed the excised tissue to be testicular. Twelve years later, she was admitted to our hospital with a lack of breast development. Her pubic hair and breasts were Tanner stage I. She had normal female external genitalia. Blood hormone tests showed normal testosterone levels, low estradiol levels, and high gonadotropin levels. Her two siblings underwent similar examinations, and all three had a rare hemizygous missense mutation in AR: c.2678C>T. In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells. CONCLUSION: This case of CAIS was caused by an AR variant (c.2678C>T). Functional studies showed impaired nuclear translocation ability of the mutant protein.

Preliminary study a non-invasion method on early cardiac energy defect based on Hilbert Huang Transform.

Statistics released by the World Health Organization in 2018 show that the total death of people is 56.9 million worldwide in 2016. The first one is cardiovascular diseases, including ischemic heart disease and stroke, which accounted for 17.65 million people (31%) [1]. Treadmill Exercise Test is suitable for measuring the changes in Electrocardiography (ECG) initial, middle, and after exercise [2]. They are using it to distinguish chest pain without apparent causes, judging the severity of coronary artery disease, and screening personnel with coronary artery disease risk factors. The most important contribution of this study is to use the Hilbert Huang Transform (HHT) [3], a non-invasive method, to decompose the original ECG signals of inspectors through the Empirical Mode Decomposition (EMD) [4-7], not the commonly used of 12-lead ECG detection method. There is a total of 49 participants in 24 pseudo-positive persons; 4 were re-judged into positive, reducing 83.3% pseudo-positive persons who need to do the follow-up testing, significantly reducing the consumption of medical and time.

New mutation in EPCAM for congenital tufting enteropathy: A case report.

BACKGROUND: Congenital tufting enteropathy (CTE) is a rare cause of diarrhea in children. However, it can result in early-onset of chronic diarrhea and failure to thrive. Children with this disease have to depend on total parenteral nutrition (TPN), and eventually small intestine transplantation. The epithelial cell adhesion molecule (EPCAM) gene was identified to be associated with CTE. Here, we present a case of an infant with CTE due to a mutation not reported in the literature before. CASE SUMMARY: A 1-year and 7-mo infant boy exhibited intractable watery diarrhea and mushy stool within 1 wk after birth, for which he had required medical treatment and hospitalization several times. His sister presented similar symptoms and died at the age of two. On admission, his body weight was 5700 g (-4.8SDS) and measured 66 cm (-5.4SDS) in height. Meanwhile, he cannot speak or climb. He exhibited mild anemia, hypocalcemia, hypomagnesemia, and an infection in the upper respiratory tract. Microvilli sparse and vacuolar degeneration of epithelial cells were reported by small intestine biopsy. Whole-exome sequencing showed a novel homozygous splice mutation (c.657+1[IVS6] G>A) in the EPCAM gene. He was treated with TPN and recombinant human growth hormone. After 2 mo, his body weight was up to 8500 g and he has been waiting for small bowel transplantation. CONCLUSION: CTE is rare but fatal. Patients with CTE require rapid diagnosis and therapy to improve their survival.

A novel semi-supervised multi-view clustering framework for screening Parkinson's disease.

In recent years, there are many research cases for the diagnosis of Parkinson's disease (PD) with the brain magnetic resonance imaging (MRI) by utilizing the traditional unsupervised machine learning methods and the supervised deep learning models. However, unsupervised learning methods are not good at extracting accurate features among MRIs and it is difficult to collect enough data in the field of PD to satisfy the need of training deep learning models. Moreover, most of the existing studies are based on single-view MRI data, of which data characteristics are not sufficient enough. In this paper, therefore, in order to tackle the drawbacks mentioned above, we propose a novel semi-supervised learning framework called Semi-supervised Multi-view learning Clustering architecture technology (SMC). The model firstly introduces the sliding window method to grasp different features, and then uses the dimensionality reduction algorithms of Linear Discriminant Analysis (LDA) to process the data with different features. Finally, the traditional single-view clustering and multi-view clustering methods are employed on multiple feature views to obtain the results. Experiments show that our proposed method is superior to the state-of-art unsupervised learning models on the clustering effect. As a result, it may be noted that, our work could contribute to improving the effectiveness of identifying PD by previous labeled and subsequent unlabeled medical MRI data in the realistic medical environment.

Novel deletion mutation in Bruton's tyrosine kinase results in X-linked agammaglobulinemia: A case report.

BACKGROUND: X-linked agammaglobulinemia is a primary immunodeficiency disease caused by gene mutations of Bruton's tyrosine kinase (BTK). We found a new mutation point and summarized the correlation analysis and performed a literature review. CASE SUMMARY: The proband was a 5-year-old boy. He was admitted to our hospital due to a recurrent cough and a fever that had persisted for a month. He had a history of multiple respiratory infections and sinusitis. There was no immunodeficiency or recurrent infection history among his family members. Agammaglobulinemia was characterized as follows: Immunoglobulin (Ig) A, 90.0 mg/dL (90-450 mg/dL); IgG, 20.0 mg/dL (800-1800 mg/dL); and IgM, 18.0 mg/dL (60-280 mg/dL). Notably, the assessment of IgG subtypes revealed the following very low levels: Subtype 1, 0.26 g/L (3.62-12.28 g/L); subtype 2, 0.10 g/L (0.57-2.9 g/L); subtype 3, 0.009 g/L (0.129-0.789 g/L); and subtype 4, 0.003 g/L (0.013-1.446 g/L). Cellular immunological test results were as follows: CD3, 74.6% (50%-84.0%); CD4, 47.3% (27.0%-51.0%); and CD8, 24.9% (15.0%-44.0%). A de novo hemizygous deletion in BTK was detected: c.902_c.904delAAG/p.E301del. Transcript levels of the mutant BTK were similar to those of the wild-type gene, though overexpression resulted in markedly reduced levels of mutant BTK (9.49% ± 1.58%), relative to the wild-type BTK (75.8% ± 2.98%, P < 0.01). CONCLUSION: This case of X-linked agammaglobulinemia was attributed to a de novo hemizygous deletion mutation in BTK (c.902_c.904delAAG/p.E301del). The mutation resulted in markedly reduced BTK protein stability in vitro.