Biallelic Loss-of-Function Variant in <i>MINPP1</i> Causes Pontocerebellar Hypoplasia with Characteristic Severe Neurodevelopmental Disorder.

ABSTRACT: Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted metabolomic analyses. The clinic

SUBMITTER: Al-Maraghi A 

PROVIDER: S-EPMC12154299 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature