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Novel Exosc9 Variants Cause Pontocerebellar Hypoplasia Type 1D With Spinal Motor Neuronopathy and Cerebellar Atrophy Publisher Pubmed



Sakamoto M1, 2 ; Iwama K1, 2 ; Sekiguchi F1 ; Mashimo H3 ; Kumada S3 ; Ishigaki K4 ; Okamoto N5 ; Behnam M6 ; Ghadami M7, 8 ; Koshimizu E1 ; Miyatake S1, 9 ; Mitsuhashi S1 ; Mizuguchi T1 ; Takata A1 Show All Authors
Authors
  1. Sakamoto M1, 2
  2. Iwama K1, 2
  3. Sekiguchi F1
  4. Mashimo H3
  5. Kumada S3
  6. Ishigaki K4
  7. Okamoto N5
  8. Behnam M6
  9. Ghadami M7, 8
  10. Koshimizu E1
  11. Miyatake S1, 9
  12. Mitsuhashi S1
  13. Mizuguchi T1
  14. Takata A1
  15. Saitsu H10
  16. Miyake N1
  17. Matsumoto N1

Source: Journal of Human Genetics Published:2021


Abstract

Pontocerebellar hypoplasia (PCH) is currently classified into 13 subgroups and many gene variants associated with PCH have been identified by next generation sequencing. PCH type 1 is a rare heterogeneous neurodegenerative disorder. The clinical presentation includes early-onset severe developmental delay, progressive motor neuronopathy, and cerebellar and pontine atrophy. Recently two variants in the EXOSC9 gene (MIM: 606180), NM_001034194.1: c.41T>C (p.Leu14Pro) and c.481C>T (p.Arg161*) were identified in four unrelated patients with PCH type 1D (PCH1D) (MIM: 618065). EXOSC9 encodes a component of the exosome complex, which is essential for correct processing and degradation of RNA. We report here two PCH1D families with biallelic EXOSC9 variants: c.239T>G (p.Leu80Arg) and c.484dupA (p.Arg162Lysfs*3) in one family and c.151G>C (p.Gly51Arg) in the other family. Although the patients studied here showed similar clinical features as previously described for PCH1D, relatively greater intellectual development (although still highly restricted) and normal pontine structure were recognized. Our findings expand the clinical consequences of biallelic EXOSC9 variants. © 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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