Heonjong Han, Go Hun Seo, Seong-In Hyun, Kisang Kwon, Seung Woo Ryu, Rin Khang, Eugene Lee, JiHye Kim, Yongjun Song, Won Chan Jeong, Joohyun Han, Dong-Wook Kim, Soyeon Yang, Sohyun Lee, Sohyun Jang, Jungsul Lee, Hane Lee
{"title":"Exome sequencing of 18,994 ethnically diverse patients with suspected rare Mendelian disorders.","authors":"Heonjong Han, Go Hun Seo, Seong-In Hyun, Kisang Kwon, Seung Woo Ryu, Rin Khang, Eugene Lee, JiHye Kim, Yongjun Song, Won Chan Jeong, Joohyun Han, Dong-Wook Kim, Soyeon Yang, Sohyun Lee, Sohyun Jang, Jungsul Lee, Hane Lee","doi":"10.1038/s41525-024-00455-3","DOIUrl":"10.1038/s41525-024-00455-3","url":null,"abstract":"<p><p>We investigated the effectiveness of exome sequencing (ES) in diagnosing ethnically diverse patients with rare genetic disorders. A total of 18,994 patients referred to a single reference laboratory for ES between 2020 and 2022 were studied for the diagnostic rate and factors influencing the diagnostic rate. The overall diagnostic rate was 31.8%. Dermatological disorders, skeletal disorders, and neurodevelopmental disorders disease categories, early age-of-onset, presence of consanguinity, and the presence of parental sequencing data were found to be correlated with a higher diagnostic rate. Nearly 68K variants were identified in our dataset at a higher frequency than that observed in gnomAD 4.0. Of these, 507 variants could be classified as likely benign, representing 0.04% of non-benign variants in ClinVar (507/1,433,904) and 0.20% of the non-benign ClinVar variants observed at least once in our cohort (507/276,777). The overall diagnostic rate is comparable to that observed in other large cohort studies with less diverse ethnic backgrounds.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Klaudia Horti-Oravecz, Anikó Bozsik, Tímea Pócza, Ildikó Vereczkey, Tamás Strausz, Erika Tóth, Tatiana Sedlackova, Diana Rusnakova, Tomas Szemes, István Likó, Edit Oláh, Henriett Butz, Attila Patócs, János Papp, Vince Kornél Grolmusz
{"title":"Whole genome sequencing completes the molecular genetic testing workflow of patients with Lynch syndrome.","authors":"Klaudia Horti-Oravecz, Anikó Bozsik, Tímea Pócza, Ildikó Vereczkey, Tamás Strausz, Erika Tóth, Tatiana Sedlackova, Diana Rusnakova, Tomas Szemes, István Likó, Edit Oláh, Henriett Butz, Attila Patócs, János Papp, Vince Kornél Grolmusz","doi":"10.1038/s41525-025-00461-z","DOIUrl":"10.1038/s41525-025-00461-z","url":null,"abstract":"<p><p>Multigene panel tests (MGPTs) revolutionized the diagnosis of Lynch syndrome (LS), however noncoding pathogenic variants (PVs) can only be detected by complementary methods including whole genome sequencing (WGS). Here we present a DNA-, RNA- and tumor tissue-based WGS prioritization workflow for patients with a suspicion of LS where MGPT detected no LS-related PV. Among the 100 enrolled patients, MGPT detected 28 simple PVs and an additional 3 complex PVs. Among the 69 MGPT-negative patients, the lack of somatic MLH1 promoter methylation in a patient with a distinguished MLH1 allelic imbalance selected this sample for WGS. This returned a germline deep intronic MLH1 variant, with further functional studies confirming its' pathogenicity. Interestingly, all three complex PVs and the MLH1 deep intronic PV were found to be recurrent at our center. Our straightforward and cost-effective prioritization workflow can optimally include WGS in the genetic diagnosis of LS.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"5"},"PeriodicalIF":4.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanno Schmidt, Lea Schick, Jürgen Podlech, Angélique Renzaho, Bettina Lieb, Stefan Diederich, Thomas Hankeln, Bodo Plachter, Oliver Kriege
{"title":"Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient.","authors":"Hanno Schmidt, Lea Schick, Jürgen Podlech, Angélique Renzaho, Bettina Lieb, Stefan Diederich, Thomas Hankeln, Bodo Plachter, Oliver Kriege","doi":"10.1038/s41525-025-00463-x","DOIUrl":"10.1038/s41525-025-00463-x","url":null,"abstract":"<p><p>Immunocompromised patients struggle to adequately clear viral infections, offering the virus the opportunity to adapt to the immune system in the host. Here we present a case study of a patient undergoing allogeneic hematopoietic stem cell transplantation with a 521-day follow-up of a SARS-CoV-2 infection with the BF.7.21 variant. Virus samples from five time points were submitted to whole genome sequencing. Between the first detection of SARS-CoV-2 infection and its clearance, the patient's virus population acquired 34 amino acid substitutions and 8 deletions in coding regions. With 11 amino acid substitutions in the receptor binding domain of the virus' spike protein, substitutions were 15 times more abundant than expected for a random distribution in this highly functional region. Amongst them were the substitutions S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, and S:E484V at positions that are notorious for their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"4"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gemma Llargués-Sistac, Laia Bonjoch, Jenifer Muñoz, Xavier Domínguez-Rovira, Teresa Ocaña, Maria Isabel Alvarez-Mora, Celia Badenas, Anna Esteve-Codina, Carlos Reyes-Silva, Gabriela Jaramillo-Koupermann, Maria Teresa Rodrigo, Sandra López-Prades, Miriam Cuatrecasas, Antoni Castells, Francesc Balaguer, Leticia Moreira, Guerau Fernandez, Sergi Castellví-Bel
{"title":"Germline structural variant as the cause of Lynch Syndrome in a family from Ecuador.","authors":"Gemma Llargués-Sistac, Laia Bonjoch, Jenifer Muñoz, Xavier Domínguez-Rovira, Teresa Ocaña, Maria Isabel Alvarez-Mora, Celia Badenas, Anna Esteve-Codina, Carlos Reyes-Silva, Gabriela Jaramillo-Koupermann, Maria Teresa Rodrigo, Sandra López-Prades, Miriam Cuatrecasas, Antoni Castells, Francesc Balaguer, Leticia Moreira, Guerau Fernandez, Sergi Castellví-Bel","doi":"10.1038/s41525-025-00462-y","DOIUrl":"10.1038/s41525-025-00462-y","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3'-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"3"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniele Merico, Nigel Sharfe, Harjit Dadi, Bhooma Thiruvahindrapuram, Jill de Rijke, Zakia Dahi, Mehdi Zarrei, Abdulrahman Al Ghamdi, Azhar Al Shaqaq, Linda Vong, Stephen W Scherer, Chaim M Roifman
{"title":"Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.","authors":"Daniele Merico, Nigel Sharfe, Harjit Dadi, Bhooma Thiruvahindrapuram, Jill de Rijke, Zakia Dahi, Mehdi Zarrei, Abdulrahman Al Ghamdi, Azhar Al Shaqaq, Linda Vong, Stephen W Scherer, Chaim M Roifman","doi":"10.1038/s41525-024-00453-5","DOIUrl":"10.1038/s41525-024-00453-5","url":null,"abstract":"<p><p>Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling. In this study, we describe the role of whole genome sequencing (WGS) in providing a definitive diagnosis for a child with T cell deficiency, where targeted panel sequencing of SCID genes and whole exome sequencing had failed. A novel homozygous 8kb deletion in PTCRA, encoding pTCRα, was identified. To date, use of WGS remains restricted and for many geographical regions, is clinically unavailable.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"2"},"PeriodicalIF":4.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deepak N Subramanian, Maia Zethoven, Kathleen I Pishas, Evanny R Marinović, Simone McInerny, Simone M Rowley, Prue E Allan, Lisa Devereux, Dane Cheasley, Paul A James, Ian G Campbell
{"title":"Assessment of candidate high-grade serous ovarian carcinoma predisposition genes through integrated germline and tumour sequencing.","authors":"Deepak N Subramanian, Maia Zethoven, Kathleen I Pishas, Evanny R Marinović, Simone McInerny, Simone M Rowley, Prue E Allan, Lisa Devereux, Dane Cheasley, Paul A James, Ian G Campbell","doi":"10.1038/s41525-024-00447-3","DOIUrl":"10.1038/s41525-024-00447-3","url":null,"abstract":"<p><p>High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-function variants. For validation, we undertook case-control analyses using genomic data from disease-free controls. This confirms enrichment for nearly all previously identified genes. Additionally, one-hundred-and-eleven HGSOC tumours from variant carriers were sequenced alongside other complementary studies, seeking evidence of biallelic inactivation as supportive evidence. PALB2 and ATM validate as HGSOC predisposition genes, with 6/8 germline carrier tumours exhibiting biallelic inactivation accompanied by characteristic mutational signatures. Among candidate genes, only LLGL2 consistently shows biallelic inactivation and protein expression loss, supporting it as a novel HGSOC susceptibility gene. The remaining candidate genes fail to validate. Integrating case-control analyses with tumour sequencing is thus crucial for accurate gene discovery in familial cancer studies.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"10 1","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ashlesha Gogate, Kiran Kaur, Raida Khalil, Mahmoud Bashtawi, Mary Ann Morris, Kimberly Goodspeed, Patricia Evans, Maria H Chahrour
{"title":"Author Correction: The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort.","authors":"Ashlesha Gogate, Kiran Kaur, Raida Khalil, Mahmoud Bashtawi, Mary Ann Morris, Kimberly Goodspeed, Patricia Evans, Maria H Chahrour","doi":"10.1038/s41525-024-00458-0","DOIUrl":"10.1038/s41525-024-00458-0","url":null,"abstract":"","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"72"},"PeriodicalIF":4.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenming Yang, Yue Yang, Han Wang, Jiuxiang Wang, Shijie Zhang
{"title":"Clinical and genetic characterization of patients with late onset Wilson's disease.","authors":"Wenming Yang, Yue Yang, Han Wang, Jiuxiang Wang, Shijie Zhang","doi":"10.1038/s41525-024-00459-z","DOIUrl":"10.1038/s41525-024-00459-z","url":null,"abstract":"<p><p>Wilson's disease (WD) typically manifests in children and young adults, with little knowledge of its late-onset forms. In this study, we performed a retrospective cohort study of 105 WD patients (99 index cases, 6 siblings) with an onset age ≥35 years. We compared 99 index late-onset patients with 1237 early-onset patients and analyzed the ATP7B variant penetrance referring to the Genome Aggregation Database (gnomAD). Sixty-two ATP7B variants were identified in the late-onset patients, among which A874V, V1106I, R919G, and T935M were correlated with late presentation of WD. Regarding gnomAD, V1106I and T935M exhibited significantly low penetrance, and there is a lack of patients carrying a genotype of V1106I/V1106I, R919G/R919G, T935M/T935M, V1106I/T935M, V1106I/R919G, or T935M/R919G. Our data revealed that patients carrying a combination of two late-onset variants may be overlooked due to atypical or lack of WD symptoms, which may provide valuable insights into the genetic basis and diagnosis of WD.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"71"},"PeriodicalIF":4.7,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amali C Mallawaarachchi, Yvonne Hort, Laura Wedd, Kitty Lo, Sarah Senum, Mojgan Toumari, Wenhan Chen, Mike Utsiwegota, Jane Mawson, Scott Leslie, Jerome Laurence, Lyndal Anderson, Paul Snelling, Robert Salomon, Gopala K Rangan, Timothy Furlong, John Shine, Mark J Cowley
{"title":"Somatic mutation in autosomal dominant polycystic kidney disease revealed by deep sequencing human kidney cysts.","authors":"Amali C Mallawaarachchi, Yvonne Hort, Laura Wedd, Kitty Lo, Sarah Senum, Mojgan Toumari, Wenhan Chen, Mike Utsiwegota, Jane Mawson, Scott Leslie, Jerome Laurence, Lyndal Anderson, Paul Snelling, Robert Salomon, Gopala K Rangan, Timothy Furlong, John Shine, Mark J Cowley","doi":"10.1038/s41525-024-00452-6","DOIUrl":"10.1038/s41525-024-00452-6","url":null,"abstract":"<p><p>Autosomal Dominant Polycystic Kidney Disease (ADPKD) results in progressive cysts that lead to kidney failure, and is caused by heterozygous germline variants in PKD1 or PKD2. Cyst pathogenesis is not definitively understood. Somatic second-hit mutations have been implicated in cyst pathogenesis, though technical sequencing challenges have limited investigation. We used unique molecular identifiers, high-depth massively parallel sequencing and custom analysis techniques to identify somatic second-hit mutations in 24 whole cysts from disparate regions of six human ADPKD kidneys, utilising replicate samples and orthogonal confirmation. Average depth of coverage of 1166 error-corrected reads for PKD1 and 539 reads for PKD2 was obtained. 58% (14/24) of cysts had a detectable PKD1 somatic variant, with 5/6 participants having at least one cyst with a somatic variant. We demonstrate that low-frequency somatic mutations are detectable in a proportion of cysts from end-stage ADPKD human kidneys. Further studies are required to understand the drivers of this somatic mutation.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"69"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simone Montalbano, Morten Dybdahl Krebs, Anders Rosengren, Morteza Vaez, Kajsa-Lotta Georgii Hellberg, Preben B Mortensen, Anders D Børglum, Daniel H Geschwind, Armin Raznahan, Wesley K Thompson, Dorte Helenius, Thomas Werge, Andrés Ingason
{"title":"Analysis of exonic deletions in a large population study provides novel insights into NRXN1 pathology.","authors":"Simone Montalbano, Morten Dybdahl Krebs, Anders Rosengren, Morteza Vaez, Kajsa-Lotta Georgii Hellberg, Preben B Mortensen, Anders D Børglum, Daniel H Geschwind, Armin Raznahan, Wesley K Thompson, Dorte Helenius, Thomas Werge, Andrés Ingason","doi":"10.1038/s41525-024-00450-8","DOIUrl":"10.1038/s41525-024-00450-8","url":null,"abstract":"<p><p>The NRXN1 locus is a hotspot for non-recurrent copy number variants and exon-disrupting NRXN1 deletions have been associated with increased risk of neurodevelopmental disorders in case-control studies. However, corresponding population-based estimates of prevalence and disease-associated risk are currently lacking. Also, most studies have not differentiated between deletions affecting exons of different NRXN1 splice variants nor considered intronic deletions. We used the iPSYCH2015 case-cohort sample to obtain unbiased estimates of the prevalence of NRXN1 deletions and their associated risk of autism, schizophrenia, depression, and ADHD. Most exon-disrupting deletions affected exons specific to the alpha isoform, and almost half of the non-exonic deletions represented a previously reported segregating founder deletion. Carriage of exon-disrupting NRXN1 deletions was associated with a threefold and twofold increased risk of autism and ADHD, respectively, whereas no significantly increased risk of depression or schizophrenia was observed. Our results highlight the importance of using population-based samples in genetic association studies.</p>","PeriodicalId":19273,"journal":{"name":"NPJ Genomic Medicine","volume":"9 1","pages":"67"},"PeriodicalIF":4.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
