Expanded PCH1D phenotype linked to EXOSC9 mutation |
| |
| Institution: | 1. Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates;2. Pediatric Department, Latifa Hospital, Dubai Health Authority, P.O.Box 4115, Dubai, United Arab Emirates;3. John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2600, Australia;1. Myelin Disorders Clinic, Pediatric Neurology Division, Children''s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;3. Department of Pediatrics, Division of Pediatric Radiology, Children''s Medical Center, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;1. Clinical Research Institute, Kanagawa Children''s Medical Center, Yokohama, Japan;2. Division of Medical Genetics, Kanagawa Children''s Medical Center, Yokohama, Japan;3. Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan;4. Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan;1. Baylor College of Medicine, Department of Pediatrics, USA;2. Baylor College of Medicine, Department of Molecular and Human Genetics, USA;3. Baylor College of Medicine, Renal Section, Department of Pediatrics, and Texas Children''s Hospital, USA;1. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan;2. Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan;3. Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan |
| |
| 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. |
| |
| Keywords: | Pontocerebellar hypoplasia EXOSC9 Neurodegenerative PCH1 PCH1D |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
