| First Author | Ghosh SG | Year | 2021 |
| Journal | Eur J Hum Genet | Volume | 29 |
| Issue | 6 | Pages | 957-964 |
| PubMed ID | 33824466 | Mgi Jnum | J:341546 |
| Mgi Id | MGI:7541153 | Doi | 10.1038/s41431-021-00832-x |
| Citation | Ghosh SG, et al. (2021) Biallelic hypomorphic mutations in HEATR5B, encoding HEAT repeat-containing protein 5B, in a neurological syndrome with pontocerebellar hypoplasia. Eur J Hum Genet 29(6):957-964 |
| abstractText | HEAT repeats are 37-47 amino acid flexible tandem repeat structural motifs occurring in a wide variety of eukaryotic proteins with diverse functions. Due to their ability to undergo elastic conformational changes, they often serve as scaffolds at sites of protein interactions. Here, we describe four affected children from two families presenting with pontocerebellar hypoplasia manifest clinically with neonatal seizures, severe intellectual disability, and motor delay. Whole exome sequencing identified biallelic variants at predicted splice sites in intron 31 of HEATR5B, encoding the HEAT repeat-containing protein 5B segregating in a recessive fashion. Aberrant splicing was found in patient fibroblasts, which correlated with reduced levels of HEATR5B protein. HEATR5B is expressed during brain development in human, and we failed to recover live-born homozygous Heatr5b knockout mice. Taken together, our results implicate loss of HEATR5B in pontocerebellar hypoplasia. |
