复合型皮质发育不良伴其他脑畸形1型患儿一例

doi:10.12280/gjszjk.20250532

国际生殖健康/计划生育杂志 ›› 2026, Vol. 45 ›› Issue (2): 116-119.doi: 10.12280/gjszjk.20250532

复合型皮质发育不良伴其他脑畸形1型患儿一例

王玉佩, 翟玺国, 张钏, 梁莉, 朱静, 惠玲()

730050 兰州，甘肃省妇幼保健院/甘肃省中心医院（王玉佩，张钏，梁莉，惠玲）; 甘肃省出生缺陷与罕见病临床医学研究中心（王玉佩，张钏，惠玲）; 西北师范大学生命科学学院（翟玺国，朱静）

收稿日期:2025-10-24 出版日期:2026-03-15 发布日期:2026-04-07
通讯作者: 惠玲 E-mail:zyhuil@hotmail.com
基金资助:
甘肃省科技计划项目(25YFFA057);甘肃省科技计划项目(23YFFA0045);甘肃省卫生健康行业科研计划项目(GSWSKY2021-021)

A Case of Complex Cortical Dysplasia with Other Brain Malformations Type 1

WANG Yu-pei, ZHAI Xi-guo, ZHANG Chuan, LIANG Li, ZHU Jing, HUI Ling()

Gansu Provincial Maternity and Child-care Hospital / Gansu Provincial Central Hospital, Lanzhou 730050, China (WANG Yu-pei, ZHANG Chuan, LIANG Li, HUI Ling); Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou 730030, China (WANG Yu-pei, ZHANG Chuan, HUI Ling);College of Life Science, Northwest Normal University, Lanzhou 730070, China (ZHAI Xi-guo, ZHU Jing)

Received:2025-10-24 Published:2026-03-15 Online:2026-04-07
Contact: HUI Ling E-mail:zyhuil@hotmail.com

摘要/Abstract

摘要：

复合型皮质发育不良伴其他脑畸形1型（complex cortical dysplasia with other brain malformations type 1，CDCBM1）是一种神经元迁移异常和轴突导向紊乱性疾病，临床表现为智力障碍、斜视、轴向张力减退和癫痫。报告1例因发育迟缓、认知障碍、脑发育异常就诊的患儿。经家系全外显子组测序、并对可疑致病变异进行Sanger测序，发现患儿TUBB3基因外显子4存在c.862G>A(p.Glu288Lys)杂合错义变异，父母均未检测出该变异。根据美国医学遗传学与基因组学学会（American College of Medical Genetics and Genomics，ACMG）评级，该变异为可能致病（PS2+PM2+PP2）。TUBB3基因编码β-Ⅲ微管蛋白（β-Ⅲ tubulin）。遗传学检测结果提示患儿为TUBB3基因c.862G>A(p.Glu288Lys)杂合错义变异导致的CDCBM1患者，为该家系的临床诊断与遗传咨询提供依据。

关键词: 皮质发育畸形, 微管蛋白, 突变, 全外显子组测序, TUBB3基因

Abstract:

Complex cortical dysplasia with other brain malformations type 1 (CDCBM1) is a disorder characterized by abnormal neuronal migration and axonal guidance defects, clinically presenting with intellectual disability, strabismus, reduced axial tone, and epilepsy. We report a case of a child presenting with developmental delay, cognitive impairment, and abnormal brain development. Trio-whole exome sequencing revealed a heterozygous missense mutation c.862G>A(p.Glu288Lys) in exon 4 of the TUBB3 gene, validated by Sanger sequencing. Neither parent carried this variant. According to the American College of Medical Genetics and Genomics (ACMG) criteria, this variant is classified as likely pathogenic (PS2+PM2+PP2). The TUBB3 gene encodes β-Ⅲ tubulin. The genetic testing results indicated that this case of CDCBM1 was caused by the heterozygous missense mutation c.862G>A(p.Glu288Lys) in TUBB3 gene, providing the evidence for the clinical diagnosis and genetic counseling of this family.

Key words: Malformations of cortical development, Tubulin, Mutation, Whole exome sequencing, TUBB3 gene

王玉佩, 翟玺国, 张钏, 梁莉, 朱静, 惠玲. 复合型皮质发育不良伴其他脑畸形1型患儿一例[J]. 国际生殖健康/计划生育杂志, 2026, 45(2): 116-119.

WANG Yu-pei, ZHAI Xi-guo, ZHANG Chuan, LIANG Li, ZHU Jing, HUI Ling. A Case of Complex Cortical Dysplasia with Other Brain Malformations Type 1[J]. Journal of International Reproductive Health/Family Planning, 2026, 45(2): 116-119.

图/表 3

图1 患儿头颅MRI 注：A 头颅中线略向左偏移，三脑室扩张，侧脑室不对称性扩张（箭头所示），基底神经节发育异常（红色虚线）；B 脑回发育不良，双侧外侧裂不对称（箭头所示），胼胝体脑回发育不良；C 脑干发育不对称（红色虚线）；D 胼胝体体部略短（箭头所示）。

图2 患儿及其父母的基因检测结果分析注：A 所研究家庭的系谱分析，箭头所示为先证者；B 通过Sanger测序验证突变，Ⅱ-1、Ⅰ-1和Ⅰ-2分别为患儿、父亲和母亲；C 不同脊椎动物TUBB3 p.288Glu位点的保守性分析。

图3 TUBB3基因突变位点蛋白结构预测注：野生型（上）和突变型（下）的三维结构中288位氨基酸变异前后残基的氢键变化。

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复合型皮质发育不良伴其他脑畸形1型患儿一例

A Case of Complex Cortical Dysplasia with Other Brain Malformations Type 1

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