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Identification of a Novel Missense Mutation of POLR3A Gene in a Cohort of Sicilian Patients with Leukodystrophy

Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathog...

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Detalles Bibliográficos
Autores principales: Musumeci, Antonino, Calì, Francesco, Scuderi, Carmela, Vinci, Mirella, Vitello, Girolamo Aurelio, Musumeci, Sebastiano Antonino, Chiavetta, Valeria, Federico, Concetta, Amore, Greta, Saccone, Salvatore, Di Rosa, Gabriella, Nicotera, Antonio Gennaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496502/
https://www.ncbi.nlm.nih.gov/pubmed/36140376
http://dx.doi.org/10.3390/biomedicines10092276
Descripción
Sumario:Recessive mutations in the POLR3A gene cause POLR3-HLD (the second-most-common form of childhood-onset hypomyelinating leukodystrophy), a neurodegenerative disorder featuring deficient cerebral myelin formation. To date, more than 140 POLR3A (NM_007055.3) missense mutations are related to the pathogenesis of POLR3-related leukodystrophy and spastic ataxia. Herein, in a cohort of five families from Sicily (Italy), we detected two cases of patients affected by POLR3-related leukodystrophy, one due to a compound heterozygous mutation in the POLR3A gene, including a previously undescribed missense mutation (c.328A > G (p.Lys110Glu)). Our study used an in-house NGS gene panel comprising 41 known leukodystrophy genes. Successively, we used a predictive test supporting the missense mutation as causative of disease, thus this mutation can be considered “Likely Pathogenic” and could be as a new pathogenetic mutation of the POLR3A gene causing a severe form of POLR3-HLD.