Identification and functional analysis of a rare variant of gene DHX37 in a patient with 46,XY disorders of sex development.

BACKGROUND: 46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD). METHODS: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting. RESULTS: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein. CONCLUSIONS: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.

Invasion by Cenchrus spinifex changes the soil microbial community structure in a sandy grassland ecosystem.

Continuous nitrogen deposition increases the nitrogen content of terrestrial ecosystems and alters the soil nitrogen cycling process. Invasive plants have strong environmental adaptability, which can not only affect the composition and diversity of soil microbial community but also significantly affect the transformation process of soil nitrogen, leading to successful invasion. Currently, research on invasive plant soil ecosystems mainly focused on changes in soil nutrients and soil microorganisms. As an invasive annual grass weed with strong ecological adaptability, the impact of Cenchrus spinifex at different growth periods on soil environment and soil microbial structure composition and diversity in sandy grassland ecosystems is still unclear. In this study, soil samples were collected from four habitats with different degrees of invasion in situ during the vegetation and reproductive growth periods of Cenchrus spinifex. High-throughput sequencing and qPCR technology were used to analyze the changes in the composition, structure and diversity characteristics of the soil microbial communities during Cenchrus spinifex invasion. The results indicated that Cenchrus spinifex invasion had different effects on the soil environment at different growth periods, and Cenchrus spinifex had a preference for the utilization of ammonium nitrogen during vegetation growth period. Moreover, Cenchrus spinifex invasion significantly changed the composition and structure of soil bacterial communities, and the response of soil bacterial and fungal communities to the invasion was inconsistent. Additionally, the bacterial network was more stable than the fungal network. At different growth periods, Cenchrus spinifex had a significant impact on the key microbial communities of soil nitrogen cycling. The invasion increased the abundance of nifH and AOA-amoA, while decreased the abundance of AOA-amoB. Alkaline hydrolyzed nitrogen, total nitrogen and total phosphorus content were key factors that affect vegetation growth period and change the key microbial communities of nitrogen cycling. Alkaline hydrolyzed nitrogen, total phosphorus and organic carbon were key factors in reproductive growth period that alter the nitrogen cycling of key microbial communities.

Correction: Deng et al. Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence in Colletotrichum gloeosporioides. J. Fungi 2023, 9, 566.

In the original publication [...].

Distinct Roles of Ena ATP Family Proteins in Sodium Accumulation, Invasive Growth, and Full Virulence in Colletotrichum gloeosporioides.

Colletotrichum gloeosporioides, a significant fungal pathogen of crops and trees, causes large economic losses worldwide. However, its pathogenic mechanism remains totally unclear. In this study, four Ena ATPases (Exitus natru-type adenosine triphosphatases), homology of yeast Ena proteins, were identified in C. gloeosporioides. Gene deletion mutants of ΔCgena1, ΔCgena2, ΔCgena3, and ΔCgena4 were obtained through the method of gene replacement. First, a subcellular localization pattern indicated that CgEna1 and CgEna4 were localized in the plasma membrane, while the CgEna2 and CgEna3 were distributed in the endoparasitic reticulum. Next, it was found that CgEna1 and CgEna4 were required for sodium accumulation in C. gloeosporioides. CgEna3 was required for extracellular ion stress of sodium and potassium. CgEna1 and CgEna3 were involved in conidial germination, appressorium formation, invasive hyphal development, and full virulence. The mutant of ΔCgena4 was more sensitive to the conditions of high concentrations of ion and the alkaline. Together, these results indicated that CgEna ATPase proteins have distinct roles in sodium accumulation, stress resistance, and full virulence in C. gloeosporioides.

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated. RESULTS: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins.

OBJECTIVES: To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation. MATERIALS AND METHODS: We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague-Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells. RESULTS: A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague-Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased. CONCLUSIONS: FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation. CLINICAL RELEVANCE: This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.

Clinical, neurophysiological evaluation and genetic features of axonal Charcot-Marie-Tooth disease in a Chinese family.

Charcot-Marie-Tooth disease (CMT) is a group of inherited peripheral neuropathies related to variants in the mitochondrial transfer RNA (mt-tRNAval) gene. Here, we report a Chinese family harboring the m.1661A>G variant in the mt-tRNAval gene. Clinical evaluation, neuroelectrodiagnostic testing, and nerve biopsy were performed on four affected family members. Weakness, spasms, and pain in the limbs (especially in the lower limbs) were the main complaints of the proband. Physical examination revealed atrophy and weakness in the distal limbs, increased muscle tone, and hyperreflexia in four limbs. Neuroelectrodiagnostic tests and nerve biopsy supported an axonal polyneuropathy. This study furthers the understanding of phenotype diversity caused by variants in the mt-tRNAval gene in CMT.

Fungus Pichia kudriavzevii XTY1 and heterotrophic nitrifying bacterium Enterobacter asburiae GS2 cannot efficiently transform organic nitrogen via hydroxylamine and nitrite.

Heterotrophic nitrification is a process of organic nitrogen degradation completed by the participation of heterotrophic nitrifying microorganisms, which can accelerate the nitrogen transformation process. However, the current research mainly focuses on heterotrophic nitrifying bacteria and their ammonium degradation capacities. And there is little accumulation of research on fungi, the main force of heterotrophic nitrification, and their capacities to transform organic nitrogen. In this study, novel heterotrophic nitrifying fungus (XTY1) and bacterium (GS2) were screened and isolated from upland soil, and the strains were identified and registered through GenBank comparison. After 24 h single nitrogen source tests and 15N labeling tests, we compared and preliminarily determined the heterotrophic nitrification capacities and pathways of the two strains. The results showed that XTY1 and GS2 had different transformation capacities to different nitrogen substrates and could efficiently transform organic nitrogen. However, the transformation capacity of XTY1 to ammonium was much lower than that of GS2. The two strains did not pass through NH2OH and NO2 - during the heterotrophic nitrification of organic nitrogen, and mainly generated intracellular nitrogen and low N2O. Other novel organic nitrogen metabolism pathways may be existed, but they remain to be further validated.

A correlation-based feature analysis of physical examination indicators can help predict the overall underlying health status using machine learning.

As a systematic investigation of the correlations between physical examination indicators (PEIs) is lacking, most PEIs are currently independently used for disease warning. This results in the general physical examination having limited diagnostic values. Here, we systematically analyzed the correlations in 221 PEIs between healthy and 34 unhealthy statuses in 803,614 individuals in China. Specifically, the study population included 711,928 healthy participants, 51,341 patients with hypertension, 12,878 patients with diabetes, and 34,997 patients with other unhealthy statuses. We found rich relevance between PEIs in the healthy physical status (7662 significant correlations, 31.5%). However, in the disease conditions, the PEI correlations changed. We focused on the difference in PEIs between healthy and 35 unhealthy physical statuses and found 1239 significant PEI differences, suggesting that they could be candidate disease markers. Finally, we established machine learning algorithms to predict health status using 15-16% of the PEIs through feature extraction, reaching a 66-99% accurate prediction, depending on the physical status. This new reference of the PEI correlation provides rich information for chronic disease diagnosis. The developed machine learning algorithms can fundamentally affect the practice of general physical examinations.

Android malware detection method based on highly distinguishable static features and DenseNet.

The rapid growth of malware has become a serious problem that threatens the security of the mobile ecosystem and needs to be studied and resolved. Android is the main target of attackers due to its open source and popularity. To solve this serious problem, an accurate and efficient malware detection method is needed. Most existing methods use a single type of feature, which can be easily bypassed, resulting in low detection accuracy. In addition, although multiple types of features are used in some methods to solve the drawbacks of detection methods using a single type of feature, there are still some problems. Firstly, due to multiple types of features, the number of features in the initial feature set is extremely large, and some methods directly use them for training, resulting in excessive overhead. Furthermore, some methods utilize feature selection to reduce the dimensionality of features, but they do not select highly distinguishable features, resulting in poor detection performance. In this article, an effective and accurate method for identifying Android malware, which is based on an analysis of the use of seven types of static features in Android is proposed to cope with the rapid increase in the amount of Android malware and overcome the drawbacks of detection methods using a single type of feature. Instead of utilizing all extracted features, we design three levels of feature selection methods to obtain highly distinguishable features that can be effective in identifying malware. Then a fully densely connected convolutional network based on DenseNet is adopted to leverage features more efficiently and effectively for malware detection. Compared with the number of features in the original feature set, the number of features in the feature set obtained by the three levels of feature selection methods is reduced by about 97%, but the accuracy is only reduced by 0.45%, and the accuracy is more than 99% in a variety of machine learning methods. Moreover, we compare our detection method with different machine learning models, and the experimental results show that our method outperforms general machine learning models. We also compare the performance of our detection method with two state-of-the-art neural networks. The experimental results show that our detection model can greatly reduce the training cost and still achieve good detection performance, reaching an accuracy of 99.72%. In addition, we compare our detection method with other similar detection methods that also use multiple types of features. The results show that our detection method is superior to the comparison methods.

Characterization of pyruvate metabolism and citric acid cycle patterns predicts response to immunotherapeutic and ferroptosis in gastric cancer.

BACKGROUND: Gastric cancer is one of the most common malignancies of the digestive system with a high lethal rate. Studies have shown that inherited and acquired mutations in pyruvate metabolism and citric acid cycle (P-CA) enzymes are involved in tumorigenesis and tumor development. However, it is unclear how different P-CA patterns affect the tumor microenvironment (TME), which is critical for cancer progression. METHODS: This study mainly concentrated on investigating the role of the P-CA patterns in multicellular immune cell infiltration of GC TME. First, the expression levels of P-CA regulators were profiled in GC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts to construct a consensus clustering analysis and identify three distinct P-CA clusters. GSVA was conducted to reveal the different biological processes in three P-CA clusters. Subsequently, 1127 cluster-related differentially expressed genes were identified, and prognostic-related genes were screened using univariate Cox regression analysis. A scoring system was then set up to quantify the P-CA gene signature and further evaluate the response of the patients to the immunotherapy. RESULTS: We found that GC patients in the high P-CA score group had a higher tumor mutational burden, higher microsatellite instability, and better prognosis. The opposite was observed in the low P-CA score group. Interestingly, we demonstrated P-CA gene cluster could predict the sensitivity to immunotherapy and ferroptosis-induced therapy. CONCLUSION: Collectively, the P-CA gene signature in this study exhibits potential roles in the tumor microenvironment and predicts the response to immunotherapeutic. The identification of these P-CA patterns may significantly accelerate the strategic development of immunotherapy for GC.

SnRK1A-mediated phosphorylation of a cytosolic ATPase positively regulates rice innate immunity and is inhibited by Ustilaginoidea virens effector SCRE1.

Rice false smut caused by Ustilaginoidea virens is becoming one of the most recalcitrant rice diseases worldwide. However, the molecular mechanisms underlying rice immunity against U. virens remain unknown. Using genetic, biochemical and disease resistance assays, we demonstrated that the xb24 knockout lines generated in non-Xa21 rice background exhibit an enhanced susceptibility to the fungal pathogens U. virens and Magnaporthe oryzae. Consistently, flg22- and chitin-induced oxidative burst and expression of pathogenesis-related genes in the xb24 knockout lines were greatly attenuated. As a central mediator of energy signaling, SnRK1A interacts with and phosphorylates XB24 at Thr83 residue to promote ATPase activity. SnRK1A is activated by pathogen-associated molecular patterns and positively regulates plant immune responses and disease resistance. Furthermore, the virulence effector SCRE1 in U. virens targets host ATPase XB24. The interaction inhibits ATPase activity of XB24 by blocking ATP binding to XB24. Meanwhile, SCRE1 outcompetes SnRK1A for XB24 binding, and thereby suppresses SnRK1A-mediated phosphorylation and ATPase activity of XB24. Our results indicate that the conserved SnRK1A-XB24 module in multiple crop plants positively contributes to plant immunity and uncover an unidentified molecular strategy to promote infection in U. virens and a novel host target in fungal pathogenesis.

Ustilaginoidea virens Nuclear Effector SCRE4 Suppresses Rice Immunity via Inhibiting Expression of a Positive Immune Regulator OsARF17.

Rice false smut caused by the biotrophic fungal pathogen Ustilaginoidea virens has become one of the most important diseases in rice. The large effector repertory in U. virens plays a crucial role in virulence. However, current knowledge of molecular mechanisms how U. virens effectors target rice immune signaling to promote infection is very limited. In this study, we identified and characterized an essential virulence effector, SCRE4 (Secreted Cysteine-Rich Effector 4), in U. virens. SCRE4 was confirmed as a secreted nuclear effector through yeast secretion, translocation assays and protein subcellular localization, as well as up-regulation during infection. The SCRE4 gene deletion attenuated the virulence of U. virens to rice. Consistently, ectopic expression of SCRE4 in rice inhibited chitin-triggered immunity and enhanced susceptibility to false smut, substantiating that SCRE4 is an essential virulence factor. Furthermore, SCRE4 transcriptionally suppressed the expression of OsARF17, an auxin response factor in rice, which positively regulates rice immune responses and resistance against U. virens. Additionally, the immunosuppressive capacity of SCRE4 depended on its nuclear localization. Therefore, we uncovered a virulence strategy in U. virens that transcriptionally suppresses the expression of the immune positive modulator OsARF17 through nucleus-localized effector SCRE4 to facilitate infection.

Ustilaginoidea virens secretes a family of phosphatases that stabilize the negative immune regulator OsMPK6 and suppress plant immunity.

Rice false smut caused by Ustilaginoidea virens is emerging as a devastating disease of rice (Oryza sativa) worldwide; however, the molecular mechanisms underlying U. virens virulence and pathogenicity remain largely unknown. Here we demonstrate that the small cysteine-rich secreted protein SCRE6 in U. virens is translocated into host cells during infection as a virulence factor. Knockout of SCRE6 leads to attenuated U. virens virulence to rice. SCRE6 and its homologs in U. virens function as a novel family of mitogen-activated protein kinase phosphatases harboring no canonical phosphatase motif. SCRE6 interacts with and dephosphorylates the negative immune regulator OsMPK6 in rice, thus enhancing its stability and suppressing plant immunity. Ectopic expression of SCRE6 in transgenic rice promotes pathogen infection by suppressing the host immune responses. Our results reveal a previously unidentified fungal infection strategy in which the pathogen deploys a family of tyrosine phosphatases to stabilize a negative immune regulator in the host plant to facilitate its infection.

Involvement of Protein Kinase CgSat4 in Potassium Uptake, Cation Tolerance, and Full Virulence in Colletotrichum gloeosporioides.

The ascomycete Colletotrichum gloeosporioides is a causal agent of anthracnose on crops and trees and causes enormous economic losses in the world. Protein kinases have been implicated in the regulation of growth and development, and responses to extracellular stimuli. However, the mechanism of the protein kinases regulating phytopathogenic fungal-specific processes is largely unclear. In the study, a serine/threonine CgSat4 was identified in C. gloeosporioides. The CgSat4 was localized in the cytoplasm. Targeted gene deletion showed that CgSat4 was essential for vegetative growth, sporulation, and full virulence. CgSat4 is involved in K+ uptake by regulating the localization and expression of the potassium transporter CgTrk1. CgSat4 is required for the cation stress resistance by altering the phosphorylation of CgHog1. Our study provides insights into potassium acquisition and the pathogenesis of C. gloeosporioides.

[Analysis of A Pedigree with Hereditary Coagulation Factor â « Deficiency Caused by Compound Heterozygous Mutations].

OBJECTIVE: To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency. METHODS: The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function. RESULTS: The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family. CONCLUSION: The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.

Effect of Ensiling Density and Storage Temperature on Fermentation Quality, Bacterial Community, and Nitrate Concentration of Sorghum-Sudangrass Silage.

This study aimed to evaluate the fermentation quality, bacterial community, and nitrate content of sorghum-sudangrass silage with two ensiling densities [550 kg fresh weight (FW)/m3 (low density, LD) and 650 kg FW/m3 (high density, HD)] stored at two temperatures [10°C (low temperature, LT) and 25°C (normal temperature, NT)] for 60 days. The fermentation parameters, microbial counts, bacterial community, nutritional composition, and nitrate and nitrite levels were assessed. The pH and ammonia nitrogen (N) in all silages were below 4.0 and 80 g/kg total N, respectively. Compared with LT treatments, NT treatments had lower pH and lactic acid (LA) bacteria and yeasts counts and contained higher LA and LA/acetic acid (LA/AA) (p < 0.05). The LT-LD contained more ammonia-N than LT-HD (p < 0.05) and had higher nitrate and lower nitrate degradation than other treatments (p < 0.05). Lactobacillus was the most dominant genus with all treatments (57.2-66.9%). The LA, LA/AA, and abundances of Pantoea, Pseudomonas, and Enterobacter in the silage negatively correlated with nitrate concentration and positively correlated with nitrate degradation (p < 0.05). Moreover, pH and ammonia-N were positively correlated with nitrate concentration and negatively correlated with nitrate degradation (p < 0.05). Overall, all silage had satisfactory fermentation quality, and the silage with HD and NT had better fermentation quality and higher nitrate degradation. The bacterial communities in all silages were dominated by Lactobacillus. The nitrate degradation during the fermentation process might be related to the fermentation quality and the activity of Pantoea, Pseudomonas, and Enterobacter in silage.

Chemical Analysis of Commercial White Wines and Its Relationship with Consumer Acceptability.

White wine consists of numerous chemical constituents such as volatile and nonvolatile compounds including organic acids and polyphenols, which can affect aroma and flavor profiles. In addition to the enological factors, chemical analysis of commercial wines is also important for understanding consumer perception. Volatile compounds are major contributors to wine aroma. Nonvolatile compounds affect the flavor of wine, through acidity, sweetness, bitterness, and astringency. The volatile aroma profiles of 12 commercial white wines were analyzed using headspace solid-phase microextraction (HS-SPME), with gas chromatography-mass spectrometry (GC-MS). High-performance liquid chromatography (HPLC) and a Y15 automatic analyzer were used to identify and quantify 10 polyphenols and 12 other target nonvolatile compounds. Sensory evaluation of sample wines was conducted by wine consumers. White wines were distinguished based on volatile and nonvolatile compositions. A total of 33 volatile compounds and 23 nonvolatile compounds were analyzed. Seven volatile compounds were correlated with consumer acceptability. Sugars are positively correlated with consumer preference, while nonvolatile substances such as acetic acid and catechins are negatively correlated with consumer preference. These results might further our understanding of the relationship between the chemical composition and consumer preferences in commercial wines.

A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China.

Aim: Hypotrichosis simplex (MIM 146520) is a rare form of monogenic hereditary alopecia. Several genes have been identified as being associated with the disease, including LPAR6, LIPH, and DSG4. LSS encoding lanosterol synthase (LSS) has been shown to cause hypotrichosis simplex, but the related mechanisms have not been elucidated to date. This study aims to find mutations in LSS from a Chinese family, among which a 21-year-old male patient and his 9-year-old sister were affected by hypotrichosis simplex. Methods: Dermoscopy and histological analysis were used to examine patients' scalps, while exome sequencing was used to find the mutations in LSS. Results: The hair loss was only detected on the scalp of the proband and his sister, while other ectodermal structures were normal with no systemic abnormalities. Further, the exome sequencing identified a new homozygous mutation NM_002340.6 (LSS_v001):c.812T>C (p.(Ile271Thr)) in the LSS gene of the proband, which was also found in his sister. In addition, a heterozygous mutation of LSS was found in their asymptomatic parents. Finally, the possible protein structure of the mutational LSS was predicted. Conclusion: The hypotrichosis simplex reported here could be an autosomal recessive disease in this family. The mutation on LSS might reduce the enzyme activity of LSS, thus leading to the disease.

[Analysis of clinical phenotype and genetic variants in a Chinese pedigree affected with Angelman syndrome].

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Angelman syndrome (AS). METHODS: The proband with phenotypes suggestive of AS was subjected to copy number variation sequencing (CNV-seq), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and high-throughput next generation sequencing (NGS). Variant of the UBE3A gene was verified among family members by Sanger sequencing and bioinformatic analysis. RESULTS: NGS revealed that the proband has carried a heterozygous variant of the UBE3A gene, namely c.1517G>A (p.R506H). The variant has co-segregated with the disease in the pedigree. Multiple amino acid sequence alignment showed that the site of mutant residue is conserved among nine homologous species. The variant was predicted to be deleterious by bioinformatic analysis. CONCLUSION: A novel variant of the UBE3A gene has been identified in a Chinese pedigree affected with AS. Above finding has further expanded the spectrum of UBE3A gene variants and phenotypes of AS, which also facilitated molecular diagnosis and genetic counseling for the family.