Guo Chong, Chen Chunmei, Wang Xinrui, Lin Kaiwu, Guo Jingmin, Ge Pin
Child Healthcare Department, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
Front Pediatr. 2025 Aug 29;13:1634704. doi: 10.3389/fped.2025.1634704. eCollection 2025.
A mutation rendering microtubulin and microtubule-associated proteins ineffective leads to a tubulinopathy known as complex cortical dysplasia (CCD), characterized by clinical heterogeneity and a variety of cortical brain developmental abnormalities. These often commence with intellectual disability, epileptic seizures, and motor disorders. In this case, we present a 6-year-old child with CCD whose symptoms began with central precocious puberty. Whole-exome sequencing uncovered a TUBB2B gene heterozygous mutation, NM_178012.5:c.74G > A (p.Ser25Asn). To our knowledge, this mutation has not been previously documented. Computational structural analysis indicated that this variant alters the hydrogen bonding between Ser25 and Trp21, Gly29, and Ile30, thus modifying the secondary structure and function of the protein, contributing to the child's unique clinical presentation. These findings expand the range of TUBB2B gene variants and offer a direction for the precise treatment of this child, underscoring the importance of brain magnetic resonance imaging in children with central precocious puberty.
一种使微管蛋白和微管相关蛋白失效的突变会导致一种称为复杂性皮质发育异常（CCD）的微管病，其特征是临床异质性和多种皮质脑发育异常。这些异常通常始于智力残疾、癫痫发作和运动障碍。在此病例中，我们报告一名6岁患有CCD的儿童，其症状始于中枢性性早熟。全外显子测序发现了一个TUBB2B基因杂合突变，NM_178012.5:c.74G＞A（p.Ser25Asn）。据我们所知，该突变此前尚未见报道。计算结构分析表明，该变体改变了Ser25与Trp21、Gly29和Ile30之间的氢键，从而改变了蛋白质的二级结构和功能，导致了该患儿独特的临床表现。这些发现扩展了TUBB2B基因变体的范围，并为该患儿的精准治疗提供了方向，强调了脑磁共振成像在中枢性性早熟儿童中的重要性。
