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A homozygous intron TUBG1 variant in Moroccan patients

elmakhzen, b.; Song, Y.; kettani, o.; EL ASRI, Y. A.; Rchiad, z.; BOUGUENOUCH, L.; Askander, O.

2025-03-13 genetic and genomic medicine
10.1101/2025.03.11.25323037 medRxiv
Show abstract

Tubulinopathies, or tubulin-related cortical dysgenesis, are a group of overlapping brain disorders caused by pathogenic mutations in tubulin-encoding genes. These disorders include microcephaly, polymicrogyria, and lissencephaly/pachygyria, which are commonly associated with severe seizures and intellectual incapacity. TUBG1, which encodes tubulin-gamma-1, is critical for microtubule nucleation at the microtubule organizing center (MTOC), which is required for neuronal development. Previously, only autosomal dominant missense variants of TUBG1 were reported, which had been predicted to act through a dominant-negative mechanism. We provide the first case of a homozygous splice variation in TUBG1 in two siblings who exhibit clinical symptoms compatible with tubulinopathy. This study increases the mutational spectrum of TUBG1 and proposes a unique recessive inheritance mechanism. Further research is needed to confirm the pathogenicity of this variation and understand the genotype-phenotype relationship.

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