Molecular characteristics
The TSEN15 (tRNA Splicing Endonuclease 15) gene is located at 1q25.3 and encodes a subunit of the tRNA splicing endonuclease complex, which is responsible for the removal of introns from tRNA precursors.
Mutations and pathophysiology
Mutations in TSEN15 result in disruption of the interacting TSEN subunits in different ways and usually lead to almost complete lack of in vitro tRNA cleavage activity.
The following are some selected examples of pathogenic variants in TSEN15:
Alazami et al. (2015) reported homozygosity for a c.226T>G mutation in TSEN15 (NM_052965.3) leading to a p.Trp76Gly. The patient was born to a consanguineous Saudi family and displayed features consistent with pontocerebellar hypoplasia type 2F.
In another similarly affected patient born to a consanguineous Pakistani family, Breuss et al. (2016) identified a homozygous a c.455A>G mutation in TSEN15 (NM_052965.3) leading to a p.Tyr152Cys substitution.
Additionally, Breuss et al. (2016) reported two brothers from a consanguineous Syrian family with pontocerebellar hypoplasia type 2F. A homozygous c.346C>T transition leading to a p.His116Tyr substitution was identified in TSEN15 (NM_052965.3).