EXOSC9 mutation causes pontocerebellar hypoplasia type 1D (PCH1D): Refining the phenotype and literature review

Pathogenic variants in EXOSC9 cause pontocerebellar hypoplasia; type 1D (PCH1D), an extremely rare autosomal recessive disorder. Herein, we report a variant in an Iranian patient (NM_001034194.2: c.151G>C, p. Gly51Arg) identified by whole-exome sequencing. Moreover, we are reporting the tenth patient with PCH1D disease in the world. The proband vary in some of his clinical features with the other reported cases. Our data, combined with the limited literature on EXOSC9 mutations, to date, support that EXOSC9 mutations are associated with a neurodevelopmental disorder characterized by hypotonia, developmental delay, and pontocerebellar hypoplasia. The main phenotypes examined in our patient are developmental delay, hypotonia, speech disorder, nystagmus, and cerebellar atrophy. Finally, we refine the phenotypes for better details in future examinations and review the clinical and molecular data of cases with PCH1D and our new case. Further studies are highly recommended concerning EXOSC9 mutations to validate this study's results and other EXOSC9 pathogenic variants to expand the knowledge needed for different clinical features of PCH1D disorder.