Biallelic truncating variants in <i>ATP9A</i> cause a novel neurodevelopmental disorder involving postnatal microcephaly and failure to thrive.

ABSTRACT:

Background

Genes implicated in the Golgi and endosomal trafficking machinery are crucial for brain development, and mutations in them are particularly associated with postnatal microcephaly (POM).

Methods

Exome sequencing was performed in three affected individuals from two unrelated consanguineous families presenting with delayed neurodevelopment, intellectual disability of variable degree, POM and failure to thrive. Patient-derived fibroblasts were tested for functional effects of the variants.

Results

We detected homozygous truncating variants in ATP9A. While the variant in family A is predicted to result in an early premature termination codon, the variant in family B affects a canonical splice site. Both variants lead to a substantial reduction of ATP9A

SUBMITTER: Vogt G 

PROVIDER: S-EPMC9252857 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature