人类染色体16p11.2综合征

doi:10.12280/gjszjk.20220073

摘要/Abstract

摘要：

16p11.2综合征是由染色体16p11.2区域缺失或重复引起的遗传性综合征,其临床表型具有广泛的异质性和不完全外显性。16p11.2微缺失综合征的表型特征是发育迟缓、智力障碍、孤独症谱系障碍和肥胖等;而16p11.2微重复综合征的临床表型特征是孤独症谱系障碍、精神分裂症、智力障碍和小头畸形等。16p11.2综合征的核心易感区是chr16：28.8~29.0 Mb（BP2-BP3）的220 kb大小的远端区域和chr16：29.6~30.2 Mb（BP4-BP5）的593 kb大小的近端区域,其主要发生机制是区域内的低拷贝重复序列通过非等位基因同源重组介导再发的基因组重排。随着染色体微阵列分析在产前诊断中的广泛应用,越来越多的微重复和微缺失综合征被发现。而16p11.2综合征尚无有效的治疗方法,因此详细了解该病的临床表型特征、发病机制、主要候选基因等,可为产前遗传咨询提供依据,从而进行生育指导。

关键词: 遗传关联研究, 产前诊断, 基因检测, 16p11.2综合征, 微缺失, 微重复

Abstract:

The 16p11.2 syndrome is caused by the microdeletion or microduplication of chromosome 16p11.2 region, which is characterized by extensive heterogeneity and incomplete penetrance. The phenotype of 16p11.2 microdeletion is characterized by developmental retardation, intellectual disability, autism spectrum disorder (ASD), and morbid obesity, while the phenotype of 16p11.2 microduplication is characterized by ASD, schizophrenia, intellectual disability and microcephaly. Two core susceptible regions of 16p11.2 are a distal breakpoints (BP) at 28.8-29.0 Mb (BP2-BP3) of 220 kb and a proximal BP at 29.6-30.2 Mb (BP4-BP5) interval of 593 kb. Recurrent rearrangements of nonallelic homologous recombination between highly similar duplicated sequences lead to the deletion or duplication of 16p11.2. With the wide application of chromosome microarray analysis as a prenatal diagnostic technique, chromosomal microdeletions and microduplications are increasingly recognized. However, there is currently no effective therapeutic method for 16p11.2 syndrome. Therefore, a detailed understanding of the clinical manifestations, mechanism and candidate genes of 16p11.2 syndrome may provide a basis for genetic counseling.

Key words: Genetic association studies, Prenatal diagnosis, Genetic testing, 16p11.2 syndrome, Microdeletion, Microduplication

杨小梅, 吴琦嫦. 人类染色体16p11.2综合征[J]. 国际生殖健康/计划生育, 2022, 41(3): 245-251.

YANG Xiao-mei, WU Qi-chang. Research Progress in Human Chromosome 16p11.2 Microdeletion and Microduplication Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(3): 245-251.

图/表 1

参考文献 36

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主要异常分类	16p11.2微缺失	16p11.2微重复
神经精神系统	微缺失携带者中有48%患有精神障碍性疾病^[3],其中ASD患病率约为22%~26%^[3,11],智力障碍约为10%~30%^[3,11],注意缺陷多动障碍约为19%~29%^[3,11],焦虑障碍约为6%~20%^[3,11],癫痫约为11%~22%^[12-13],对立违抗性障碍约为13%~39%^[3,11],震颤约为8%^[12]、行为障碍约为13%^[11],学习障碍约为13%^[11],抽动障碍约为6%^[11],言语缺陷约为71%~94%^[3,11]。	微重复携带者中有63%患有精神障碍性疾病^[3],其中ASD患病率约为26%^[3],智力障碍34%^[3],注意缺陷多动障碍30%~42%^[3,13],焦虑障碍12%^[3],癫痫10%~29%^[3,13],对立违抗性障碍12%~40%^[3,20],震颤28%^[12],语言及言语缺陷80%^[20];微重复携带者还可能患有精神分裂症、厌食症等。
内分泌	严重肥胖、胰岛素抵抗、肥胖	BMI下降
生长发育	巨头畸形	小头畸形
其他系统	脊柱侧弯、听力下降、中耳炎、冠心病、胃食管反流、痢疾、便秘	脊柱侧弯、肾脏和尿道的畸形、视力问题、听力下降、颌面部畸形、冠心病、胃食管反流
肿瘤	精原细胞瘤、胆脂瘤、硬纤维瘤、平滑肌瘤和肾母细胞瘤、原发性颅内生殖细胞瘤	暂无报道

主要异常分类	16p11.2微缺失	16p11.2微重复
神经精神系统	微缺失携带者中有48%患有精神障碍性疾病^[3],其中ASD患病率约为22%~26%^[3,11],智力障碍约为10%~30%^[3,11],注意缺陷多动障碍约为19%~29%^[3,11],焦虑障碍约为6%~20%^[3,11],癫痫约为11%~22%^[12-13],对立违抗性障碍约为13%~39%^[3,11],震颤约为8%^[12]、行为障碍约为13%^[11],学习障碍约为13%^[11],抽动障碍约为6%^[11],言语缺陷约为71%~94%^[3,11]。	微重复携带者中有63%患有精神障碍性疾病^[3],其中ASD患病率约为26%^[3],智力障碍34%^[3],注意缺陷多动障碍30%~42%^[3,13],焦虑障碍12%^[3],癫痫10%~29%^[3,13],对立违抗性障碍12%~40%^[3,20],震颤28%^[12],语言及言语缺陷80%^[20];微重复携带者还可能患有精神分裂症、厌食症等。
内分泌	严重肥胖、胰岛素抵抗、肥胖	BMI下降
生长发育	巨头畸形	小头畸形
其他系统	脊柱侧弯、听力下降、中耳炎、冠心病、胃食管反流、痢疾、便秘	脊柱侧弯、肾脏和尿道的畸形、视力问题、听力下降、颌面部畸形、冠心病、胃食管反流
肿瘤	精原细胞瘤、胆脂瘤、硬纤维瘤、平滑肌瘤和肾母细胞瘤、原发性颅内生殖细胞瘤	暂无报道