Background Kabuki syndrome(KS),is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase(KMT2D)or an X-linked histone H3 lysine 27 demethylase(UTX/KDM6A).The characteristics in pat...Background Kabuki syndrome(KS),is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase(KMT2D)or an X-linked histone H3 lysine 27 demethylase(UTX/KDM6A).The characteristics in patients with KS have not yet been well recognized.Data sources We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome.The most relevant articles to the scope of this review were chosen for analysis.Results Clinical diagnosis of KS is challenging in initial period,because many clinical characteristics become apparent only in subsequent years.Recently,the genetic and functional interaction between KS-associated genes and their products have been elucidated.New clinical findings were reported including nervous system and intellectual performance,endo-crine-related disorders and immune deficiency and autoimmune disease.Cancer risks of Kabuki syndrome was reviewed.Meanwhile,we discussed the Kabuki-like syndrome.Digital clinical genetic service,such as dysmorphology database can improve availability and provide high-quality diagnostic services.Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk,efforts in the research for new mechanisms are thus of maximum interest.Conclusions Kabuki syndrome has a strong clinical and biological heterogeneity.The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and-off of the chromatin.The direction of drug research may be to regulate the normal opening of chromatin.Small molecule inhibitors of histone deacetylases maybe helpful in treatment of mental retardation and reduce cancer risk in KS.展开更多
The study reports a case of a 5-year-old Chinese girl diagnosed with Kabuki make-up Syndrome(KMS).The patient showed classic KMS appearance:widely separated eyes,ectropion of lateral one-third lower eyelids,flat nasal...The study reports a case of a 5-year-old Chinese girl diagnosed with Kabuki make-up Syndrome(KMS).The patient showed classic KMS appearance:widely separated eyes,ectropion of lateral one-third lower eyelids,flat nasal tip,and prominent ears.Auditory features in this individual included bilateral severe sensorineural hearing loss and lack of 40 Hz AERP responses identified at I year of age.The individual received cochlear implant(CI) in the left ear when 5 years old.and rehabilitation after CI treatment were 3 in speech intelligibility and 5 in auditory performance.Thus,our findings suggest that cochlear implant may be helpful to restore hearing for individuals with Kabuki syndrome.展开更多
Kabuki syndrome(MIM 147920)is an autosomal dominant rare disease featured with multiple malformations and mental retardation.The main clinical manifestations of Kabuki syndrome are characteristic facial features,skele...Kabuki syndrome(MIM 147920)is an autosomal dominant rare disease featured with multiple malformations and mental retardation.The main clinical manifestations of Kabuki syndrome are characteristic facial features,skeletal abnormalities,dermatoglyphic abnormalities,postpartum growth retardation,mild to moderate mental retardation,as well as other structural and functional abnormalities that may involve multiple systems.The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation.Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients,few prenatal diagnosis cases of Kabuki syndrome had been reported,which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis.This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites,thickening of local skin,and cardiac abnormalities.We ruled out intrauterine infection,thalassemia,and chromosome abnormality by corresponding tests.Finally,trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g>A(p.r5214h)in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome.This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites.Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities,and a multidisciplinary team is necessary for providing pregnancy guidance to patients.展开更多
Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritiz...Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.展开更多
基金the Clinical Research Promotion Project of Shanghai Jiao Tong University(no.JQ201810).
文摘Background Kabuki syndrome(KS),is a infrequent inherited malformation syndrome caused by mutations in a H3 lysine 4 methylase(KMT2D)or an X-linked histone H3 lysine 27 demethylase(UTX/KDM6A).The characteristics in patients with KS have not yet been well recognized.Data sources We used databases including PubMed and Google Scholar to search for publications about the clinical features and the etiology of Kabuki syndrome.The most relevant articles to the scope of this review were chosen for analysis.Results Clinical diagnosis of KS is challenging in initial period,because many clinical characteristics become apparent only in subsequent years.Recently,the genetic and functional interaction between KS-associated genes and their products have been elucidated.New clinical findings were reported including nervous system and intellectual performance,endo-crine-related disorders and immune deficiency and autoimmune disease.Cancer risks of Kabuki syndrome was reviewed.Meanwhile,we discussed the Kabuki-like syndrome.Digital clinical genetic service,such as dysmorphology database can improve availability and provide high-quality diagnostic services.Given the significant clinical relevance of KS-associated genes and epigenetic modifications crosstalk,efforts in the research for new mechanisms are thus of maximum interest.Conclusions Kabuki syndrome has a strong clinical and biological heterogeneity.The main pathogenesis of Kabuki syndrome is the imbalance between switch-on and-off of the chromatin.The direction of drug research may be to regulate the normal opening of chromatin.Small molecule inhibitors of histone deacetylases maybe helpful in treatment of mental retardation and reduce cancer risk in KS.
文摘The study reports a case of a 5-year-old Chinese girl diagnosed with Kabuki make-up Syndrome(KMS).The patient showed classic KMS appearance:widely separated eyes,ectropion of lateral one-third lower eyelids,flat nasal tip,and prominent ears.Auditory features in this individual included bilateral severe sensorineural hearing loss and lack of 40 Hz AERP responses identified at I year of age.The individual received cochlear implant(CI) in the left ear when 5 years old.and rehabilitation after CI treatment were 3 in speech intelligibility and 5 in auditory performance.Thus,our findings suggest that cochlear implant may be helpful to restore hearing for individuals with Kabuki syndrome.
基金supported by the Military Medicine Innovation Project(No.17JS001 and 18JS007),China.
文摘Kabuki syndrome(MIM 147920)is an autosomal dominant rare disease featured with multiple malformations and mental retardation.The main clinical manifestations of Kabuki syndrome are characteristic facial features,skeletal abnormalities,dermatoglyphic abnormalities,postpartum growth retardation,mild to moderate mental retardation,as well as other structural and functional abnormalities that may involve multiple systems.The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation.Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients,few prenatal diagnosis cases of Kabuki syndrome had been reported,which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis.This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites,thickening of local skin,and cardiac abnormalities.We ruled out intrauterine infection,thalassemia,and chromosome abnormality by corresponding tests.Finally,trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g>A(p.r5214h)in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome.This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites.Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities,and a multidisciplinary team is necessary for providing pregnancy guidance to patients.
基金supported by the National Natural Science Foundation of China(No.81471506,81401219,81501276,and 81771638)the National Key Research and Development Program of China(No.2016YFC0905103)+4 种基金the Shanghai Municipal Commission of Science and Technology Program,China(No.15411966700,15411964000,and 17411972900)the Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai,China(No.2018YQ39)the Shanghai Municipal Commission of Health and Family Planning Program,China(No.20154Y0039 and 15GWZK0701)the Shanghai Jiao Tong University Program,China(No.YG2017MS39)the Innovation Foundation of Translational Medicine of Shanghai Jiao Tong University School of Medicine,Shanghai SJTUSM Biobank,China(No.15ZH4011).
文摘Kabuki syndrome(KS)is a rare congenital mental retardation condition characterized by facial dysmorphia,visceral and skeletal malformations,and developmental delay.The integrated phenotype and genotype-based prioritization is critical for diagnoses of genetic diseases.In this study,a Chinese woman,presenting with characteristic facial features of KS,came for pre-pregnancy consultation.We aimed to clarify the diagnosis and provide pre-pregnancy genetic counseling.Facial dysmorphology analysis and next-generation sequencing-based multigene panel approach were used to identify candidate syndromes and causative variants,respectively.The candidate variant was verified by Sanger sequencing.We identified a novel de novo KDM6A pathogenic variant(c.3521G>A)in the woman,which was in line with the Face2Gene analysis result.Peripheral blood RNA assay showed that the variant transcript underwent the nonsense-mediated mRNA decay and led to subsequent haploinsufficiency of KDM6A.Our study provides the genetic diagnosis method for KS type 2 and identifies the first KDM6A point variant in Chinese patient.
