Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Hearing Disorders: HELP
Articles by Xun Xu
Based on 5 articles published since 2010
(Why 5 articles?)
||||

Between 2010 and 2020, Xun Xu wrote the following 5 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China. 2019

Wang, Qiuju / Xiang, Jiale / Sun, Jun / Yang, Yun / Guan, Jing / Wang, Dayong / Song, Cui / Guo, Ling / Wang, Hongyang / Chen, Yaqiu / Leng, Junhong / Wang, Xiaman / Zhang, Junqing / Han, Bing / Zou, Jing / Yan, Chengbin / Zhao, Lidong / Luo, Hongyu / Han, Yuan / Yuan, Wen / Zhang, Hongyun / Wang, Wei / Wang, Jian / Yang, Huanming / Xu, Xun / Yin, Ye / Morton, Cynthia C / Zhao, Lijian / Zhu, Shida / Shen, Jun / Peng, Zhiyu. ·Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · BGI Genomics, BGI-Shenzhen, Shenzhen, China. · Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, China. · Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin, China. · Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Children's Hospital of Chongqing Medical University, Chongqing, China. · Jining Maternal and Child Health Care Service Center, Jining, China. · Tianjin Women and Children's Health Centre, Tianjing, China. · BGI Clinical Laboratory, BGI-Shenzhen, Shenzhen, China. · MGI, BGI-Shenzhen, Shenzhen, China. · Wuhan BGI Clinical Laboratory, BGI-Shenzhen, Wuhan, China. · BGI-Beijing, BGI-Shenzhen, Beijing, China. · BGI-Shenzhen, Shenzhen, China. · James D. Watson Institute of Genome Sciences, Hangzhou, China. · China National GeneBank, BGI-Shenzhen, Shenzhen, China. · Manchester Center for Audiology and Deafness, School of Health Sciences, University of Manchester, Manchester, UK. · Broad Institute of Harvard and MIT, Cambridge, MA, USA. · BGI Clinical Laboratory, BGI-Shenzhen, Shenzhen, China. zhaolijian@bgi.com. · BGI-Shenzhen, Shenzhen, China. zhushida@genomics.cn. · China National GeneBank, BGI-Shenzhen, Shenzhen, China. zhushida@genomics.cn. · Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, Shenzhen, China. zhushida@genomics.cn. · Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jshen5@bwh.harvard.edu. · BGI Genomics, BGI-Shenzhen, Shenzhen, China. pengzhiyu@bgi.com. ·Genet Med · Pubmed #30890784.

ABSTRACT: PURPOSE: The benefits of concurrent newborn hearing and genetic screening have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of newborns with genetic screening results. METHODS: Newborns in China were screened for 20 hearing-loss-related genetic variants from 2012 to 2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed up via phone interviews. RESULTS: Following up 12,778 of 1.2 million genetically screened newborns revealed a higher rate of hearing loss by three months of age among referrals from the initial hearing screening (60% vs. 5.0%, P < 0.001) and a lower rate of lost-to-follow-up/documentation (5% vs. 22%, P < 0.001) in the positive group than in the inconclusive group. Importantly, genetic screening detected 13% more hearing-impaired infants than hearing screening alone and identified 2,638 (0.23% of total) newborns predisposed to preventable ototoxicity undetectable by hearing screening. CONCLUSION: Incorporating genetic screening improves the effectiveness of newborn hearing screening programs by elucidating etiologies, discerning high-risk subgroups for vigilant management, identifying additional children who may benefit from early intervention, and informing at-risk newborns and their maternal relatives of increased susceptibility to ototoxicity.

2 Article Mutation in mitochondrial ribosomal protein S7 (MRPS7) causes congenital sensorineural deafness, progressive hepatic and renal failure and lactic acidemia. 2015

Menezes, Minal J / Guo, Yiran / Zhang, Jianguo / Riley, Lisa G / Cooper, Sandra T / Thorburn, David R / Li, Jiankang / Dong, Daoyuan / Li, Zhijun / Glessner, Joseph / Davis, Ryan L / Sue, Carolyn M / Alexander, Stephen I / Arbuckle, Susan / Kirwan, Paul / Keating, Brendan J / Xu, Xun / Hakonarson, Hakon / Christodoulou, John. ·Genetic Metabolic Disorders Research Unit, Discipline of Paediatrics and Child Health and. · The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. · T-Life Research Center, Fudan University, Shanghai 200433, China, BGI-Shenzhen, Shenzhen 518083, China. · Institute for Neuroscience and Muscle Research, Discipline of Paediatrics and Child Health and. · Murdoch Children's Research Institute and Victorian Clinical Genetics Services, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, VIC 3052, Australia, Department of Paediatrics, University of Melbourne, Melbourne, VIC 3010, Australia. · BGI-Shenzhen, Shenzhen 518083, China. · Department of Chemistry and Biochemistry, University of Sciences, Philadelphia, PA, USA. · Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, Australia. · Centre for Kidney Research and Discipline of Paediatrics and Child Health and. · Histopathology Department, Children's Hospital at Westmead 2145, Sydney, Australia. · Electron Microscopy Unit, Department of Anatomical Pathology, Concord Repatriation General Hospital, Concord, Sydney, Australia. · The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA, Department of Pediatrics and Department of Human Genetics, The Perelmen School of Medicine, University of Pennsylvania, Philadelphia, PA, USA and. · Genetic Metabolic Disorders Research Unit, Discipline of Paediatrics and Child Health and Discipline of Genetic Medicine, University of Sydney, Sydney, NSW 2006, Australia, john.christodoulou@health.nsw.gov.au. ·Hum Mol Genet · Pubmed #25556185.

ABSTRACT: Functional defects of the mitochondrial translation machinery, as a result of mutations in nuclear-encoded genes, have been associated with combined oxidative phosphorylation (OXPHOS) deficiencies. We report siblings with congenital sensorineural deafness and lactic acidemia in association with combined respiratory chain (RC) deficiencies of complexes I, III and IV observed in fibroblasts and liver. One of the siblings had a more severe phenotype showing progressive hepatic and renal failure. Whole-exome sequencing revealed a homozygous mutation in the gene encoding mitochondrial ribosomal protein S7 (MRPS7), a c.550A>G transition that encodes a substitution of valine for a highly conserved methionine (p.Met184Val) in both affected siblings. MRPS7 is a 12S ribosomal RNA-binding subunit of the small mitochondrial ribosomal subunit, and is required for the assembly of the small ribosomal subunit. Pulse labeling of mitochondrial protein synthesis products revealed impaired mitochondrial protein synthesis in patient fibroblasts. Exogenous expression of wild-type MRPS7 in patient fibroblasts rescued complexes I and IV activities, demonstrating the deleterious effect of the mutation on RC function. Moreover, reduced 12S rRNA transcript levels observed in the patient's fibroblasts were also restored to normal levels by exogenous expression of wild-type MRPS7. Our data demonstrate the pathogenicity of the identified MRPS7 mutation as a novel cause of mitochondrial RC dysfunction, congenital sensorineural deafness and progressive hepatic and renal failure.

3 Article The expanding spectrum of PRPS1-associated phenotypes: three novel mutations segregating with X-linked hearing loss and mild peripheral neuropathy. 2015

Robusto, Michela / Fang, Mingyan / Asselta, Rosanna / Castorina, Pierangela / Previtali, Stefano C / Caccia, Sonia / Benzoni, Elena / De Cristofaro, Raimondo / Yu, Cong / Cesarani, Antonio / Liu, Xuanzhu / Li, Wangsheng / Primignani, Paola / Ambrosetti, Umberto / Xu, Xun / Duga, Stefano / Soldà, Giulia. ·Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy. · BGI-Shenzhen, Shenzhen, China. · Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Audiologia, Milan, Italy. · Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy. · Laboratory of Medical Genetics, Molecular Genetic Sector, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. · Haemostasis Research Center, Institute of Internal Medicine and Geriatrics, Catholic University School of Medicine, Rome, Italy. ·Eur J Hum Genet · Pubmed #25182139.

ABSTRACT: Next-generation sequencing is currently the technology of choice for gene/mutation discovery in genetically-heterogeneous disorders, such as inherited sensorineural hearing loss (HL). Whole-exome sequencing of a single Italian proband affected by non-syndromic HL identified a novel missense variant within the PRPS1 gene (NM_002764.3:c.337G>T (p.A113S)) segregating with post-lingual, bilateral, progressive deafness in the proband's family. Defects in this gene, encoding the phosphoribosyl pyrophosphate synthetase 1 (PRS-I) enzyme, determine either X-linked syndromic conditions associated with hearing impairment (eg, Arts syndrome and Charcot-Marie-Tooth neuropathy type X-5) or non-syndromic HL (DFNX1). A subsequent screening of the entire PRPS1 gene in 16 unrelated probands from X-linked deaf families led to the discovery of two additional missense variants (c.343A>G (p.M115V) and c.925G>T (p.V309F)) segregating with hearing impairment, and associated with mildly-symptomatic peripheral neuropathy. All three variants result in a marked reduction (>60%) of the PRS-I activity in the patients' erythrocytes, with c.343A>G (p.M115V) and c.925G>T (p.V309F) affecting more severely the enzyme function. Our data significantly expand the current spectrum of pathogenic variants in PRPS1, confirming that they are associated with a continuum disease spectrum, thus stressing the importance of functional studies and detailed clinical investigations for genotype-phenotype correlation.

4 Article Expanding the phenotype of PRPS1 syndromes in females: neuropathy, hearing loss and retinopathy. 2014

Almoguera, Berta / He, Sijie / Corton, Marta / Fernandez-San Jose, Patricia / Blanco-Kelly, Fiona / López-Molina, Maria Isabel / García-Sandoval, Blanca / Del Val, Javier / Guo, Yiran / Tian, Lifeng / Liu, Xuanzhu / Guan, Liping / Torres, Rosa J / Puig, Juan G / Hakonarson, Hakon / Xu, Xun / Keating, Brendan / Ayuso, Carmen. ·Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. castillob@email.chop.edu. · College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. hesijie@genomics.cn. · BGI-Shenzhen, Shenzhen, 518083, China. hesijie@genomics.cn. · Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital (IISFJD, UAM), 28040, Madrid, Spain. mcorton@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. mcorton@fjd.es. · Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital (IISFJD, UAM), 28040, Madrid, Spain. patricia.fernandez@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. patricia.fernandez@fjd.es. · Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital (IISFJD, UAM), 28040, Madrid, Spain. fblancok@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. fblancok@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. milopez@fjd.es. · Department of Ophthalmology, Fundación Jiménez Díaz, 28040, Madrid, Spain. milopez@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. bgarcia@fjd.es. · Department of Ophthalmology, Fundación Jiménez Díaz, 28040, Madrid, Spain. bgarcia@fjd.es. · Department of Neurology, Fundación Jiménez Díaz, 28040, Madrid, Spain. JdelVal@fjd.es. · Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. guoy@email.chop.edu. · Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. tianl@email.chop.edu. · BGI-Shenzhen, Shenzhen, 518083, China. liuxuanzhu@genomics.cn. · BGI-Shenzhen, Shenzhen, 518083, China. guanliping@genomics.cn. · Department of Biochemistry, La Paz University Hospital IdiPaz, Madrid, 28046, Spain. rosa.torres@salud.madrid.org. · Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital IdiPaz, Madrid, 28046, Spain. juangarciapuig@gmail.com. · Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. hakonarson@email.chop.edu. · BGI-Shenzhen, Shenzhen, 518083, China. xuxun@genomics.cn. · The Guangdong Enterprise Key Laboratory of Human Disease Genomics, Shenzhen, China. xuxun@genomics.cn. · Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. bkeating@mail.med.upenn.edu. · Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital (IISFJD, UAM), 28040, Madrid, Spain. cayuso@fjd.es. · Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. cayuso@fjd.es. ·Orphanet J Rare Dis · Pubmed #25491489.

ABSTRACT: BACKGROUND: Phosphoribosyl pyrophosphate synthetase (PRS) I deficiency is a rare medical condition caused by missense mutations in PRPS1 that lead to three different phenotypes: Arts Syndrome (MIM 301835), X-linked Charcot-Marie-Tooth (CMTX5, MIM 311070) or X-linked non-syndromic sensorineural deafness (DFN2, MIM 304500). All three are X-linked recessively inherited and males affected display variable degree of central and peripheral neuropathy. We applied whole exome sequencing to a three-generation family with optic atrophy followed by retinitis pigmentosa (RP) in all three cases, and ataxia, progressive peripheral neuropathy and hearing loss with variable presentation. METHODS: Whole exome sequencing was performed in two affecteds and one unaffected member of the family. Sanger sequencing was used to validate and segregate the 12 candidate mutations in the family and to confirm the absence of the novel variant in PRPS1 in 191 controls. The pathogenic role of the novel mutation in PRPS1 was assessed in silico and confirmed by enzymatic determination of PRS activity, mRNA expression and sequencing, and X-chromosome inactivation. RESULTS: A novel missense mutation was identified in PRPS1 in the affected females. Age of onset, presentation and severity of the phenotype are highly variable in the family: both the proband and her mother have neurological and ophthalmological symptoms, whereas the phenotype of the affected sister is milder and currently confined to the eye. Moreover, only the proband displayed a complete lack of expression of the wild type allele in leukocytes that seems to correlate with the degree of PRS deficiency and the severity of the phenotype. Interestingly, optic atrophy and RP are the only common manifestations to all three females and the only phenotype correlating with the degree of enzyme deficiency. CONCLUSIONS: These results are in line with recent evidence of the existence of intermediate phenotypes in PRS-I deficiency syndromes and demonstrate that females can exhibit a disease phenotype as severe and complex as their male counterparts.

5 Article Noninvasive prenatal testing for autosomal recessive conditions by maternal plasma sequencing in a case of congenital deafness. 2014

Meng, Meng / Li, Xuchao / Ge, Huijuan / Chen, Fang / Han, Mingyu / Zhang, Yanyan / Kang, Dongyang / Xie, Weiwei / Gao, Zhiying / Pan, Xiaoyu / Dai, Pu / Chi, Fanglu / Chen, Shengpei / Liu, Ping / Zhang, Chunlei / Cao, Jianjun / Jiang, Hui / Xu, Xun / Wang, Wei / Duan, Tao. ·Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China. · BGI-Shenzhen, Shenzhen, China. · 1] BGI-Shenzhen, Shenzhen, China [2] Department of Biology, University of Copenhagen, Copenhagen, Denmark. · Chinese PLA General Hospital, Beijing, China. · Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China. · 1] BGI-Shenzhen, Shenzhen, China [2] BGI-Shanghai, BGI-Shenzhen, Shenzhen, China. · 1] BGI-Shenzhen, Shenzhen, China [2] Shenzhen Birth Defect Screening Project Lab, BGI-Shenzhen, Shenzhen, China. · 1] BGI-Shenzhen, Shenzhen, China [2] Clinical Laboratory of BGI Health, Shenzhen, China. ·Genet Med · Pubmed #24830326.

ABSTRACT: PURPOSE: The goals of our study were to develop a noninvasive prenatal test for autosomal recessive monogenic conditions and to prove its overall feasibility and potential for clinical integration. METHODS: We recruited a pregnant woman and her spouse, who had a proband child suffering from congenital deafness, and obtained the target-region sequencing data from a semicustom array that used genomic and maternal plasma DNA from three generations of this family. A haplotype-assisted strategy was developed to detect whether the fetus inherited the pathogenic mutations in the causative gene, GJB2. The parental haplotype was constructed using a trio strategy through two different processes, namely, the grandparent-assisted haplotype phasing process and the proband-assisted haplotype phasing process. The fetal haplotype was deduced afterward based on both the maternal plasma sequencing data and the parental haplotype. RESULTS: The accuracy levels of paternal and maternal haplotypes obtained by grandparent-assisted haplotype phasing were 99.01 and 97.36%, respectively, and the proband-assisted haplotype phasing process yielded slightly lower accuracies of 98.73 and 96.79%, respectively. Fetal inheritance of the pathogenic gene was deduced correctly in both processes. CONCLUSION: Our study indicates that the strategy of haplotype-based noninvasive prenatal testing for monogenic conditions has potential applications in clinical practice.