Bizzari Sami, Hamzeh Abdul Rezzak, Mohamed Madiha, Al-Ali Mahmoud Taleb, Bastaki Fatma
Centre for Arab Genomic Studies, P.O. Box 22252, Dubai, United Arab Emirates.
John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2600, Australia.
Eur J Med Genet. 2020 Jan;63(1):103622. doi: 10.1016/j.ejmg.2019.01.012. Epub 2019 Jan 25.
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.
1型脑桥小脑发育不全是一种罕见的异质性神经退行性疾病，有多种亚型与外泌体复合物功能障碍相关。外泌体亚基发生突变的患者通常表现出致命的表型，其特征为小脑和脑桥发育不全，并伴有脊髓运动神经病以及多种全身和神经特征。最近，在4名无亲缘关系的患者中发现了新型PCH1相关蛋白EXOSC9的两个变体，即p.(Leu14Pro)和p.(Arg161*)，这些患者表现出严重的表型，包括小脑发育不全、轴索性运动神经病、肌张力减退、喂养困难和呼吸功能不全（PCH1D）。我们报告了2名无亲缘关系患者的临床和分子特征，他们表现出相对较轻的表型，包括肌张力减退、短头畸形、小脑萎缩、精神运动发育迟缓，以及乳酸酸中毒和中枢神经系统髓鞘异常，这是由EXOSC9基因中反复出现的纯合错义突变NM_001034194.1:c.41T>C；p.(Leu14Pro)导致的。我们回顾了与EXOSC9相关的PCH疾病的临床表现。
