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Expanded PCH1D phenotype linked to EXOSC9 mutation.

Authors
  • Bizzari, Sami1
  • Hamzeh, Abdul Rezzak2
  • Mohamed, Madiha3
  • Al-Ali, Mahmoud Taleb4
  • Bastaki, Fatma3
  • 1 Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates. Electronic address: [email protected] , (United Arab Emirates)
  • 2 John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2600, Australia. , (Australia)
  • 3 Pediatric Department, Latifa Hospital, Dubai Health Authority, P.O.Box 4115, Dubai, United Arab Emirates. , (United Arab Emirates)
  • 4 Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates. , (United Arab Emirates)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Jan 01, 2020
Volume
63
Issue
1
Pages
103622–103622
Identifiers
DOI: 10.1016/j.ejmg.2019.01.012
PMID: 30690203
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pontocerebellar Hypoplasia type 1 is a rare heterogeneous neurodegenerative disorder with multiple subtypes linked to dysfunction of the exosome complex. Patients with mutations in exosome subunits exhibit a generally lethal phenotype characterized by cerebellar and pontine hypoplasia in association with spinal motor neuropathy and multiple systemic and neurologic features. Recently, two variants in the novel PCH1 associated protein EXOSC9 p.(Leu14Pro) and p.(Arg161*) have been identified in 4 unrelated patients exhibiting a severe phenotype involving cerebellar hypoplasia, axonal motor neuropathy, hypotonia, feeding difficulties, and respiratory insufficiency (PCH1D). We report clinical and molecular characterization of 2 unrelated patients exhibiting a relatively milder phenotype involving hypotonia, brachycephaly, cerebellar atrophy, psychomotor delay, as well as lactic acidosis and aberrant CNS myelination, resulting from the recurring homozygous missense mutation NM_001034194.1: c.41T>C; p.(Leu14Pro) in the EXOSC9 gene. We review the clinical picture of the EXOSC9-related PCH disorder. Copyright © 2019. Published by Elsevier Masson SAS.

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