EEFSEC deficiency underlies a human selenopathy with primary neurodevelopmental origins via midbrain-hindbrain hypoplasia.

ABSTRACT: Bi-allelic mutations in EEFSEC, a key factor in selenoprotein synthesis, cause a severe human selenopathy characterized by developmental delay, spasticity, and profound cerebellar atrophy. While previous studies in invertebrate models framed this condition as an early-onset neurodegenerative disorder, the contribution of primary developmental defects to the severe brain malformations in patients has remained a critical unanswered question. Here, we address this gap using a zebrafish model of EEFSEC deficiency. We discovered that loss of eefsec function does not impair global somatic growth but instead causes specific and significant hypoplasia of the midbrain and hindbrain-the embryonic precursors to the human cerebellum and brain stem. These structural defects directly correlate with robu

SUBMITTER: Xia Z 

PROVIDER: S-EPMC12861234 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature