Abstract
Neurodevelopmental disorder caused by malformations of cortical development is a rare neurological disease. Heterozygous missense variants in the TUBG1 gene lead to malformations of human cortical development, which further result in intellectual disability, developmental retardation, and epilepsy. To the best of our knowledge, only thirteen patients and a total of nine pathogenic TUBG1 variants have been described in the published literature. This study reports the case details and genetic data analysis of a girl (aged 8 years, 9 months) with developmental delay, psychomotor regression, epilepsy, and left external ear deformity. A novel TUBG1 mutation was identified by whole-exome sequencing and Sanger sequencing, confirming that this mutation may be the cause of the neurodevelopmental disorders. This case report characterizes the phenotypic spectrum, molecular genetic findings, and functional consequences of novel pathogenic TUBG1 variants in neurodevelopmental disorders caused by cortical development malformations.
Highlights
Neurodevelopmental disorders caused by malformations of cortical development (MCD) are rare diseases with high clinical heterogeneity
We describe a novel pathogenic variant of the TUBG1 gene (c.751A>T p.N251Y) identified through whole-exome sequencing (WES) in a Chinese patient who presented epilepsy, intellectual disability, speech impairment, and left external ear deformity; these findings may serve to improve diagnosis, management, and research on neurodevelopmental disorders caused by MCD
The parent of the patients did not present the variant by WES, so the de novo variant was verified by Sanger sequencing (Figure 3(a)) and was not detected in the published database
Summary
Neurodevelopmental disorders caused by malformations of cortical development (MCD) are rare diseases with high clinical heterogeneity. The main clinical features of MCD include motor impairment, intellectual disability, early-onset epilepsy, and cortical malformations (including lissencephaly, polymicrogyria, microlissencephaly, pachygyria, and simplified gyration) [1, 2]. The cortical and extracortical brain phenotypes observed are largely dependent on the specific tubulin gene affected. Tubulin genes play a key role in several pathways of cortical development. Mutations in these genes may cause specific brain malformations strictly associated with epilepsy [4]. Mutations affecting seven genes encoding alpha(TUBA1A), beta- (TUBB2A, TUBB2B, TUBB3, TUBB4A, and TUBB), and gamma-tubulin (TUBG1) have been identified in individuals with a range of malformations of cortical development (MCDs) [5]
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