This report describes pontocerebellar hypoplasia, TSEN54-related (TSEN54-PCH). The TSEN54 gene is implicated in multiple forms of this disease, including pontocerebellar hypoplasia, type 4 (MIM:225753, FBhh0001451), pontocerebellar hypoplasia, type 2A (MIM:277470, FBhh0001452) and pontocerebellar hypoplasia, type 5 (MIM:610204, FBhh0001453); all exhibit autosomal recessive inheritance. TSEN54 encodes a subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNAs that contain introns. There is a single orthologous gene in Drosophila, Dmel\Tsen54, for which a number genetic reagents have been generated including RNAi targeting constructs and alleles caused by insertional mutagenesis.
The human TSEN54 gene has not been introduced into flies.
Animals homozygous for loss-of-function Tsen54 alleles typically die during the larval or pupal stage. An overall reduction in brain lobe size is observed in mutant larval brains; larval locomotion is reduced.
[updated April 2022 by FlyBase; FBrf0222196]
Multiple subtypes of pontocerebellar hypoplasia have been described. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood. [MedlinePlus, Pontocerebellar hypoplasia; 2022.04.16]
Pontocerebellar hypoplasia (PCH) refers to a group of severe neurodegenerative disorders affecting growth and function of the brainstem and cerebellum, resulting in abnormally small cerebellum and brainstem. [from MIM:607596; 2022.04.16]
TSEN54 pontocerebellar hypoplasia (TSEN54-PCH) comprises three PCH phenotypes (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three PCH phenotypes (which differ mainly in life expectancy) were considered to be distinct entities before their molecular basis was known. [Gene Reviews, TSEN54 Pontocerebellar Hypoplasia; 2022.04.16]
TSEN54 encodes a non-catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. [Gene Cards, TSEN54; 2022.04.16]
In metazoans, although most tRNA genes are intronless, a subset contains introns (FBrf0253008 and references cited therein).
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human TSEN54 (1 Drosophila to 1 human).
