Abstract
The TUBGCP6 gene (22q13.33) encodes the tubulin gamma complex–associated protein 6 (TUBGCP6), which plays an essential role in centrosome function. Biallelic TUBGCP6 variants cause an ultrarare disease with microcephaly, neurodevelopmental delay, and chorioretinopathy. We report a 5-year-old boy with a novel homozygous TUBGCP6 variant and review previously reported cases.
The patient presented with global developmental delay, neurosensorial hearing loss, infantile spasms, and dysmorphic features. Brain magnetic resonance imaging showed corpus callosum and brainstem hypoplasia. Nerve conduction study revealed mild demyelinating sensory neuropathy. Trio whole-exome sequencing (WES) identified a novel TUBGCP6 variant, c.3914C>A (p.Ala1305Glu), classified as a hot variant of uncertain significance (VUS) and predicted likely deleterious.
Eighteen cases have been described in the literature with various brain malformation (lissencephaly, corpus callosum abnormalities, and cerebellar atrophy). Our report confirms that TUBGCP6 has an important role in brain development and, when defective, can cause variable patterns of brain malformations associated with complex neurodevelopmental disorders.
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