title: Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2.
abstract: Pontocerebellar hypoplasias represent a group of neurodegenerative autosomal recessive disorders characterized by hypoplasia/atrophy of the cerebellum, hypoplastic ventral pons, and microcephaly and associated with various clinical features. Pontocerebellar hypolasia type 2 is the most common form, and different mutations in genes encoding subunits of the transfer ribonucleic acid (RNA)-splicing endonuclease (TSEN) complex were identified in patients. The authors report clinical, imaging, and molecular studies in 2 unrelated patients with different clinical pictures of the pontocerebellar hypoplasia type 2 spectrum and novel mutations in TSEN54, aiming to further define the clinical spectrum of the disease and possible indicators of more favorable progression. They identified a novel missense mutation c.355T>G/p.Y119D in compound heterozygosity with the "common" c.919G>T/p.A307S (patient 1) and a novel homozygous c.7ins6(CCGGAG)/p.E2-P3insPE variant (patient 2). An expanded array of mutations might contribute in defining possible differences in severity and phenotype-genotype correlations.
authors: *These authors equally contributed to the paper.
authors: Roberta
authors: R
authors: Battini
authors: Stefano
authors: S
authors: D'Arrigo
authors: Denise
authors: D
authors: Cassandrini
authors: Andrea
authors: A
authors: Guzzetta
authors: Chiara
authors: C
authors: Fiorillo
authors: Chiara
authors: C
authors: Pantaleoni
authors: Alessandro
authors: A
authors: Romano
authors: Enrico
authors: E
authors: Alfei
authors: Giovanni
authors: G
authors: Cioni
authors: Filippo M
authors: FM
authors: Santorelli
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D009849:Olivopontocerebellar Atrophies / Q000175:diagnosis / Q000235:genetics*
chemical_list: D004722:Endoribonucleases; C559616:TSEN54 protein, human
keywords:   TSEN54 gene; genotype-phenotype correlation; microcephaly; modeling; novel mutations; pontocerebellar hypoplasia