KCNQ4 gene mutation can lead to deafness non-syndromic autosomal dominant 2A,which is a type of autosomal dominant non-syndromic hearing loss.Deafness non-syndromic autosomal dominant 2A patients with KCNQ4 gene mutat...KCNQ4 gene mutation can lead to deafness non-syndromic autosomal dominant 2A,which is a type of autosomal dominant non-syndromic hearing loss.Deafness non-syndromic autosomal dominant 2A patients with KCNQ4 gene mutation usually present with symmetrical,delayed,progressive high-frequency-affected hearing loss,which eventually can involve all frequencies.In this article,we comprehensively reviewed the research on the role and function of KCNQ4 gene in genetic hearing loss.We discussed the pathological and physiological mechanisms of KCNQ4 gene and the related clinical phenotypes of KCNQ4 gene mutations.We also reviewed the latest developments in the treatment of KCNQ4 gene mutation-related genetic hearing loss,including selective potassium channel activation drugs and gene therapy.展开更多
Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt ...Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt identification and individualized therapies.Diagnosing hearing loss in newborns is challenging,especially in mild or progressive cases,and its management requires a multidisciplinary team of healthcare providers comprising audiologists,pediatricians,otolaryngologists,and genetic counselors.While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before,a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality.In this review,we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.展开更多
Sensorineural hearing loss is the most common sensory deficit in humans,with an estimated prevalence of 1 in 500 newborns.Approximately half of childhood hearing loss is attributed to genetic factors and can be classi...Sensorineural hearing loss is the most common sensory deficit in humans,with an estimated prevalence of 1 in 500 newborns.Approximately half of childhood hearing loss is attributed to genetic factors and can be classified as syndromic or non-syndromic based on the inheritance pattern.The ion channel genesKCNQ1,KCNE1,KCNQ4,P2RX2,TMC1,KCNJ10,andCACNA1D have frequently been associated with genetic hearing loss.Because of the important roles these genes play in cochlear hair cell function and the auditory pathways,mutations in these genes that result in impaired ion channel function can lead to hereditary hearing loss.The main purpose of this review was to examine the latest research progress on the functional roles,inheritance pattern,gene expression,protein structure,clinical phenotypes,mouse models,and possible treatments of the most commonly studied ion channels associated with inherited deafness.A comprehensive summary could help highlight ion channels that should be investigated as potential drug targets for the treatment of inherited deafness.展开更多
Precision medicine（PM） proposes customized medical care based on a patient＇s unique genome, biomarkers, environment and behaviors. Hearing loss（HL） is the most common sensorineural disorder worldwide and is frequ...Precision medicine（PM） proposes customized medical care based on a patient＇s unique genome, biomarkers, environment and behaviors. Hearing loss（HL） is the most common sensorineural disorder worldwide and is frequently caused by a single genetic mutation. With recent advances in PM tools such as genetic sequencing and data analysis, the field of HL is ideally positioned to adopt the strategies of PM.Here, we review current and future applications of PM in HL as they relate to the four core qualities of PM（P4）： predictive, personalized, patient-centered, and participatory. We then introduce a strategy for effective incorporation of HL PM into the design of future research studies, electronic medical records,and clinical practice to improve diagnostics, prognostics, and, ultimately, individualized patient treatment. Finally, specific anticipated ethical and economic concerns in this growing era of genomics-based HL treatment are discussed. By integrating PM principles into translational HL research and clinical practice, hearing specialists are uniquely positioned to effectively treat the heterogeneous causes and manifestations of HL on an individualized basis.展开更多
基金supported by the grants of the National Natural Science Foundation of China(Major Project No.81830028,Youths Program Nos.81900950 and 81900951).
文摘KCNQ4 gene mutation can lead to deafness non-syndromic autosomal dominant 2A,which is a type of autosomal dominant non-syndromic hearing loss.Deafness non-syndromic autosomal dominant 2A patients with KCNQ4 gene mutation usually present with symmetrical,delayed,progressive high-frequency-affected hearing loss,which eventually can involve all frequencies.In this article,we comprehensively reviewed the research on the role and function of KCNQ4 gene in genetic hearing loss.We discussed the pathological and physiological mechanisms of KCNQ4 gene and the related clinical phenotypes of KCNQ4 gene mutations.We also reviewed the latest developments in the treatment of KCNQ4 gene mutation-related genetic hearing loss,including selective potassium channel activation drugs and gene therapy.
基金This project was supported by NIH-NIDCD(Grants No.R01 DC002842,DC012049,and DC017955)(RJHS)NIH-NIDCD(Grant No.5T32DC000040)(RKT).
文摘Hearing loss is the most common neurosensory deficit.It results froma variety of heritable and acquired causes and is linked to multiple deleterious effects on a child’s development that can be ameliorated by prompt identification and individualized therapies.Diagnosing hearing loss in newborns is challenging,especially in mild or progressive cases,and its management requires a multidisciplinary team of healthcare providers comprising audiologists,pediatricians,otolaryngologists,and genetic counselors.While physiologic newborn hearing screening has resulted in earlier diagnosis of hearing loss than ever before,a growing body of knowledge supports the concurrent implementation of genetic and cytomegalovirus testing to offset the limitations inherent to a singular screening modality.In this review,we discuss the contemporary role of screening for hearing loss in newborns as well as future directions in its diagnosis and treatment.
基金supported by funds from the National Key R&D Program of China Project(No.2017YFA0103900)the National Natural Science Foundation of China(Nos.31571083,31970931)+2 种基金the Program for Professor of Special Appointment(Eastern Scholar of Shanghai,No.TP2014008)the Shanghai Municipal Science and Technology Major Project(Nos.2017SHZDZX01 and 2018SHZDZX01)ZJLab,and the Shanghai Rising-Star Program(No.14QA1400800).
文摘Sensorineural hearing loss is the most common sensory deficit in humans,with an estimated prevalence of 1 in 500 newborns.Approximately half of childhood hearing loss is attributed to genetic factors and can be classified as syndromic or non-syndromic based on the inheritance pattern.The ion channel genesKCNQ1,KCNE1,KCNQ4,P2RX2,TMC1,KCNJ10,andCACNA1D have frequently been associated with genetic hearing loss.Because of the important roles these genes play in cochlear hair cell function and the auditory pathways,mutations in these genes that result in impaired ion channel function can lead to hereditary hearing loss.The main purpose of this review was to examine the latest research progress on the functional roles,inheritance pattern,gene expression,protein structure,clinical phenotypes,mouse models,and possible treatments of the most commonly studied ion channels associated with inherited deafness.A comprehensive summary could help highlight ion channels that should be investigated as potential drug targets for the treatment of inherited deafness.
基金supported by grants from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders(R01 DC05575, R01 DC01246 and R01 DC012115)
文摘Precision medicine（PM） proposes customized medical care based on a patient＇s unique genome, biomarkers, environment and behaviors. Hearing loss（HL） is the most common sensorineural disorder worldwide and is frequently caused by a single genetic mutation. With recent advances in PM tools such as genetic sequencing and data analysis, the field of HL is ideally positioned to adopt the strategies of PM.Here, we review current and future applications of PM in HL as they relate to the four core qualities of PM（P4）： predictive, personalized, patient-centered, and participatory. We then introduce a strategy for effective incorporation of HL PM into the design of future research studies, electronic medical records,and clinical practice to improve diagnostics, prognostics, and, ultimately, individualized patient treatment. Finally, specific anticipated ethical and economic concerns in this growing era of genomics-based HL treatment are discussed. By integrating PM principles into translational HL research and clinical practice, hearing specialists are uniquely positioned to effectively treat the heterogeneous causes and manifestations of HL on an individualized basis.
