Proteomics

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Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)


ABSTRACT: TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Neuromuscular Disease

SUBMITTER: Andreas Hentschel  

LAB HEAD: Andreas Hentschel

PROVIDER: PXD023584 | Pride | 2022-02-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20200728_144326_NME_VNFibros_45-16.sne Other
Lumos09591_KO.raw Raw
Lumos09592_45-16_1.raw Raw
Lumos09593_45-16_2.raw Raw
Lumos09594_45-16_3.raw Raw
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Publications

Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1).

Töpf Ana A   Pyle Angela A   Griffin Helen H   Matalonga Leslie L   Schon Katherine K   Sickmann Albert A   Schara-Schmidt Ulrike U   Hentschel Andreas A   Chinnery Patrick F PF   Kölbel Heike H   Roos Andreas A   Horvath Rita R  

European journal of human genetics : EJHG 20210601 9


TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome  ...[more]

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