AIM:To reveal a novel MITF gene mutation in Waardenburg syndrome(WS),which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities...AIM:To reveal a novel MITF gene mutation in Waardenburg syndrome(WS),which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes,hair and skin.METHODS:The genetic analysis of the Chinese family was conducted by whole-exome sequencing,then the results were confirmed by Sanger sequencing.RESULTS:WS is classified into type I to IV,which are identified by the W index,clinical characteristics and additional features.The MITF gene mostly accounts for WS type II.In this study,a de novo heterozygous mutation in the MITF gene,c.638 A>G in exon 7,was identified in the patient diagnosed with WS type I features,as the W index was 2.17(over 2.10),with dystrophia canthorum,congenital bilateral profound hearing loss,bilateral heterochromia irides,premature greying of the hair,and excessive freckling on the face at birth.She also underwent refractive errors and esotropia,reduced pigmentation of the choroid and visible choroid vessels.The mutation was not found in previous studies or mutation databases.CONCLUSION:The novel mutation in the MITF gene,which altered the protein in amino acids 213 from the glutamic acid to glycine,is the genetic pathological cause for WS features in the patient.Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS,which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities.Moreover,ocular symptoms should be emphasized in all types of WS patients.展开更多
强直性肌营养不良1型(myotonic dystrophy type 1,DM1)为罕见的常染色体显性遗传性疾病。中南大学湘雅三医院内分泌科收治1例以早发糖尿病和肌力下降为表现的DM1患者。采集患者外周血提取DNA进行基因检测,发现患者强直性肌营养不良蛋白...强直性肌营养不良1型(myotonic dystrophy type 1,DM1)为罕见的常染色体显性遗传性疾病。中南大学湘雅三医院内分泌科收治1例以早发糖尿病和肌力下降为表现的DM1患者。采集患者外周血提取DNA进行基因检测,发现患者强直性肌营养不良蛋白激酶(dystrophia myotonica protein kinase,DMPK)基因的3'-非翻译区(3'-untranslated region,3'-UTR)的三核苷酸CTG重复大于100次,DM1诊断明确。对于合并肌肉症状等多系统异常的糖尿病患者,应当注意DM1这一罕见疾病的筛查。展开更多
基金Supported by the National Natural Science Foundation of China(No.81800807No.81670834+2 种基金No.81970781No.81800869)the Natural Science Foundation of Zhejiang Province(No.LY17H090004)。
文摘AIM:To reveal a novel MITF gene mutation in Waardenburg syndrome(WS),which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes,hair and skin.METHODS:The genetic analysis of the Chinese family was conducted by whole-exome sequencing,then the results were confirmed by Sanger sequencing.RESULTS:WS is classified into type I to IV,which are identified by the W index,clinical characteristics and additional features.The MITF gene mostly accounts for WS type II.In this study,a de novo heterozygous mutation in the MITF gene,c.638 A>G in exon 7,was identified in the patient diagnosed with WS type I features,as the W index was 2.17(over 2.10),with dystrophia canthorum,congenital bilateral profound hearing loss,bilateral heterochromia irides,premature greying of the hair,and excessive freckling on the face at birth.She also underwent refractive errors and esotropia,reduced pigmentation of the choroid and visible choroid vessels.The mutation was not found in previous studies or mutation databases.CONCLUSION:The novel mutation in the MITF gene,which altered the protein in amino acids 213 from the glutamic acid to glycine,is the genetic pathological cause for WS features in the patient.Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS,which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities.Moreover,ocular symptoms should be emphasized in all types of WS patients.
文摘强直性肌营养不良1型(myotonic dystrophy type 1,DM1)为罕见的常染色体显性遗传性疾病。中南大学湘雅三医院内分泌科收治1例以早发糖尿病和肌力下降为表现的DM1患者。采集患者外周血提取DNA进行基因检测,发现患者强直性肌营养不良蛋白激酶(dystrophia myotonica protein kinase,DMPK)基因的3'-非翻译区(3'-untranslated region,3'-UTR)的三核苷酸CTG重复大于100次,DM1诊断明确。对于合并肌肉症状等多系统异常的糖尿病患者,应当注意DM1这一罕见疾病的筛查。
