遗传 ›› 2017, Vol. 39 ›› Issue (6): 455-468.doi: 10.16288/j.yczz.16-407

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X染色体变异对男性精神发育迟滞致病性的研究进展

彭继苹(),刘芳,谢华,陈晓丽()   

  1. 首都儿科研究所儿童发育营养组学北京市重点实验室,北京100020
  • 收稿日期:2016-11-30 修回日期:2017-01-23 出版日期:2017-06-20 发布日期:2017-03-20
  • 作者简介:彭继苹,硕士研究生,专业方向：分子遗传学。E-mail: 945180106@qq.com|陈晓丽，博士，博士生导师，研究方向：分子遗传学。E-mail: cxlwx@sina.com
  • 基金资助:
    国家自然科学基金面上项目(31671310);北京市自然科学基金面上项目(7162029);北京市百千万人才工程创新研发类项目和首都卫生发展科研专项项目(2014-2-1131)

The pathogenicity of genomic/genetic variant of X-chromosomal genes in males with intellectual disability

Jiping Peng(),Fang Liu,Hua Xie,Xiaoli Chen()   

  1. Beijing Municipal Key Laboratory of Child Development and Nutriomics, Beijing 100020, China
  • Received:2016-11-30 Revised:2017-01-23 Online:2017-06-20 Published:2017-03-20
  • Supported by:
    the National Nature Science Foundation of China(31671310);the National Nature Science Foundation of Beijing(7162029);the Innovation Project of Beijing Municipal Human Resources and Social Secutity Bureauand the Capital Health Research and Development of Special(2014-2-1131)

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摘要：

精神发育迟滞(旧称智力低下)作为儿科神经科常见的一组疾患,具有高度的遗传和表型异质性,大约25%~50%的精神发育迟滞是由遗传因素引起的,其中X染色体基因/基因组变异占25%~30%,导致X连锁的精神发育迟滞。X连锁的精神发育迟滞患者占所有精神发育迟滞患者的10%~15％以上,约20%~25％的男性精神发育迟滞归因于X连锁的精神发育迟滞。精神发育迟滞男女患病比例为1.3:1,这与男性只有一条X染色体的遗传背景有关。随着新一代基因组检测技术的快速发展和临床应用,尤其是全外显子测序、高深度测序、X染色体深度测序和全基因组芯片杂交,这些大大改善了精神发育迟滞患者的X染色体基因/基因组变异检出。本文综述了致精神发育迟滞的X染色体基因组/基因变异特点、其对男性精神发育迟滞的致病性,以及如何采用新测序技术提高检出率,旨在促进科研人员认识X染色体变异在男性精神发育迟滞的致病性,拓宽精神发育迟滞遗传病因的认识,同时也为遗传咨询和产前诊断提供理论依据。

关键词: 男性精神发育迟滞, X染色体变异, 拷贝数变异, 单核苷酸变异

Abstract:

Intellectual Disability (ID, previously named mental retardation) is a group of common pediatric neurology disorders characterized by extensive genetic and phenotypic heterogeneity. About 25%-50% of ID was caused by genomic/genetic variants, in which genomic/genetic variants of X-chromosome are one of key pathogenic causation (25%-30%), resulting in X-linked ID (XLID). The epidemiological data showed that the male to female ratio is 1.3: 1 in ID patients. The prevalence of XLID in the whole ID population is 10%-15%, and this prevalence reaches 20%-25% in the male ID population. This sex-related differential proportion of ID may be attributed to hemizygosity of X chromosomes in males. A quick detection of genomic/genetic aberrations of X chromosome is feasible and available now due to the overwhelming development of next-generation genomic techniques and their clinical applications; in particular, whole exome sequencing, customer-designed whole genomic chip for the X chromosome, high-density target sequencing and whole X chromosomal sequencing are used widely for clinical diagnosis. In this review, we systematically summarize the pathogenicity and characteristics of X-chromosomal genomic/genetic aberrations in the male patients with ID, and how the new technologies have been used to detect X-chromosomal abnormalities. This review will help researchers understand the pathogenicity of X-chromosomal variations in male ID patients from the view of whole genome, refresh the knowledge about the genomic/genetic etiology of ID, and further provide a theoretical basis for genetic counseling and prenatal diagnosis in the future.

Key words: males with intellectual disability, X-chromosomal variations, copy number variants, single nucleotide variants