These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [One novel pathologic variation in KMT2D cause Kabuki syndrome with hearing loss as the main phenotype and related research on types of deafness].
    Author: Qiu SW, Yuan YY.
    Journal: Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi; 2019 Sep; 33(9):820-824. PubMed ID: 31446696.
    Abstract:
    Objective:To make the molecular diagnosis of a patient complaining hearing loss and with specific facial features, developmental delay, vertebral dysplasia, hypotonia and other suspected phenotypes of Kabuki make-up syndrome（KS）; to investigate the characteristics and main phenotypes of KS. Method:①Whole-exome sequencing and bioinformatics analysis were performed for proband and her parents. ②Literatures describing the clinical features of KS patients with clear molecular diagnosis from the period of Aug 2010 to Mar 2019 were collected from databases of PubMed and CNKI. Result:①The proband carries the c. 15777insT variant（p. Pro5260fs*10） in KMT2D gene. The variant causes the termination codon to appear prematurely. KMT2D c. 15777insT was classified as PVS1+PS1+PM2 according to the ACMG variation interpretation standard, which is a disease-causing mutation. The c. 15777insT was first reported as a pathogenic mutation of KS. ②77 peer-reviewed publications on KS were analysed including 462 patients with KS. The main findings were intellectual disability（305 cases）, congenital heart defects（227 cases）, hypotonia（184 cases）, short fingers（147 cases）, short stature（144 cases）, cleft palate（139 cases）, hearing loss（101 cases） and developmental delay（99 cases）. Of the 101 patients with hearing loss, 11 were confirmed to have conductive hearing loss（1 with recurrent otitis media）, 3 with mixed hearing loss, 12 with sensorineural deafness（1 with recurrence otitis media） and 75 patients with unidentified types of deafness（28 with recurrent otitis media）. Conclusion:KS involves defects of a wide range of organs, with each organ showing different severity of symptoms, which is easily misdiagnosed from the phenotypes. We suggest the diagnosis on hearing loss in KS patients should be strengthened. KMT2D and KDM6A are two pathogenic genes that have been identified for KS. With the increase of age, its typical clinical phenotypes become more and more obvious. When there is only atypical suspected KS symptoms in the early neonatal period, relevant genetic test should be performed as soon as possible to achieve early diagnosis and intervention. 目的：对表现出特殊面容、发育迟缓、智力低下、椎骨发育异常、肌张力低等疑似歌舞伎脸谱综合征（Kabuki综合征，KS）表型的1例耳聋患儿进行分子检测，明确疾病病因；通过回顾性系统分析，了解KS主要表型及合并耳聋症状的特点及发生频率。 方法：①提取先证者及其父母血液DNA并进行全外显子组测序，结合可能的遗传类型对测序结果进行生物信息学分析、锁定致病突变；②检索Pubmed、中国知网数据库，对2010-08-2019-03首次明确KS分子病因的报道中所描述的KS临床特征进行筛选、归纳和总结。 结果：①基因检测显示先证者携带KMT2D基因c.15777insT变异（p.Pro5260fs*10），该变异为移码变异，导致终止密码子提前出现，按ACMG变异解读标准将其分类为PVS1+PS1+PM2，属于致病突变。KMT2D基因c.15777insT首次报道为KS的致病突变位点。②归纳出77篇符合条件的文献，结合本文1例患儿，共收集462例KS患者信息，主要表现为智力障碍（305例）、先天性心脏缺损（227例）、张力减退（184例）、短指（147例）、身材矮小（144例）、腭裂（139例）、听力下降（101例）以及发育迟缓（99例）。101例听力下降的KS患者中，有11例明确为传导性听力下降（1例伴复发性中耳炎）、3例明确为混合性听力下降、12例明确为感音神经性听力下降（1例伴复发性中耳炎）、75例听力下降类型不明（28例伴复发性中耳炎）。 结论：KS涉及的器官较为广泛，各器官症状严重程度不一，仅从表型上判断容易存在误诊和漏诊的风险。应加强对KS患者在听力学方面的诊断和关注。KMT2D和KDM6A是已明确KS的2个致病基因。KS患者从出生开始，年龄越大，其典型临床表型越明显。当新生儿早期仅仅出现不典型的疑似KS症状时，也应该尽早完善相关基因检测，实现早诊断、早干预。.
    [Abstract] [Full Text] [Related] [New Search]