Research Progress in Human Chromosome 16p11.2 Microdeletion and Microduplication Syndrome

doi:10.12280/gjszjk.20220073

Abstract

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

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.

Figures/Tables 1

References 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