Biallelic SEPSECS variants in two siblings with pontocerebellar hypoplasia type 2D underscore the relevance of splice-disrupting synonymous variants in disease.

ABSTRACT: Noncoding and synonymous coding variants that exert their effects via alternative splicing are increasingly recognized as an important category of disease-causing variants. In this report, we describe two siblings who presented with hypotonia, profound developmental delays, and seizures. Brain magnetic resonance imaging (MRI) in the proband at 5 yr showed diffuse cerebral and cerebellar white matter volume loss. Both siblings later developed ventilator-dependent respiratory insufficiency and scoliosis and are currently nonverbal and nonambulatory. Extensive molecular testing including oligo array and clinical exome sequencing was nondiagnostic. Research genome sequencing under an institutional review board (IRB)-approved study protocol revealed that both affected children were compound-het

SUBMITTER: Ramadesikan S 

PROVIDER: S-EPMC8958912 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature