Novel missense heterozygous MACF1 variant in a patient with global developmental delay, lissencephaly and drug-resistant epilepsy
Belyaeva E.O., Fonova E.A., Minaycheva L.I., Sivokha V.M., Kraeva L.S.,. Torkhova Y.B., Lopatkina M.Y., Sivtsev A.A., Zarubin A.A., Babushkina N.P., Lebedev I.N.
Discover Medicine. 2025. 2, 43.
DOI: 10.1007/s44337-025-00243-7
We report a novel variant in the MACF1 gene that caused a congenital brain anomaly (lissencephaly, brainstem hypoplasia, and agenesis of the corpus callosum) in a patient with severe neurodevelopmental delay and drug-resistant epilepsy. The patient was nonresponsive, nonverbal, and nonambulatory and experienced daily generalized myoclonic seizures, generalized muscle weakness, dysphagia, and faecal and urinary incontinence. Whole-exome sequencing revealed a missense heterozygous MACF1 variant, c.21878A>G (p.Asp7293Gly). The de novo origin of the variant was confrmed by trio Sanger sequencing. The variant was not reported previously in the gnomAD, ExAC, and 1000 Genomes databases. Our report expands the genetic heterogeneity of a rare type of lissencephaly.