Abstract
Biallelic mutations in the TRAPPC12 gene are responsible for early-onset progressive encephalopathy with brain atrophy
and spasticity (PEBAS). To date, three different allelic variants have been reported.
Next-generation sequencing allowed discovery of unique alternations in this gene with
different phenotypes. We report two patients carrying TRAPPC12 variants, one previously
reported and one unknown mutation, with severe neurodevelopmental delay and brain
atrophy. Standard clinical examination and cranial imaging studies were performed
in these two unrelated patients. In addition, whole-exome sequencing was performed,
followed by Sanger sequencing for verification. The first patient, a 2-year-old boy,
was found to be homozygous for the previously reported c.1880C > T (p.Ala627Val) mutation.
He presented with a phenotype including severe progressive cortical atrophy, moderate
cerebellar atrophy, epilepsy, and microcephaly, very similar to the previously reported
cases. The second case, a 9-year-old boy, carried a novel homozygous c.679T > G (p.Phe227Val)
variant and presented with mild cortical atrophy, severe cerebellar atrophy, and neither
clinically manifest epilepsy nor microcephaly, which were previously considered typical
findings in PEBAS with TRAPPC12 mutations. Our findings suggest that clinical and
brain imaging findings might be more variable than previously anticipated; however,
a larger number of observations would benefit for broader phenotypic spectrum.
Keywords
brain atrophy - cerebellar atrophy - microcephaly - TRAPPopathies - TRAPPC12 mutation
