Identification of pathogenic C9orf72 hexanucleotide repeat expansion in a Chinese patient with frontotemporal dementia: A case report

• Published in: CNS neuroscience & therapeutics 2021-06, Vol.27 (6), p.725-727
• Main Authors: Xue, Yan‐Yan, Wu, Zhi‐Ying, Li, Hong‐Fu
• Format: Article
• Language: English
• Subjects: Adult; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyotrophic lateral sclerosis; Antisense oligonucleotides; Asians; Atrophy; C9orf72 Protein - genetics; Cerebrospinal fluid; Dementia; Dementia disorders; DNA Repeat Expansion - genetics; Dysphagia; Electromyography; Family medical history; Female; Frontotemporal dementia; Frontotemporal Dementia - genetics; Humans; Letter to the Editor; Magnetic Resonance Imaging; Mental disorders; Motor neuron diseases; Muscular dystrophy; Patients; Pedigree; Peptide Fragments - cerebrospinal fluid; Phenotypes; Regulatory sequences; tau Proteins - cerebrospinal fluid; Toxicity
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.13639

The discovery that abnormal GGGGCC hexanucleotide repeat expansions (HRE) in C9orf72 was a common cause of FTD and amyotrophic lateral sclerosis (ALS) fueled and speeded up the research in C9orf72‐related ALS and FTD worldwide. 1,2 This pathogenic expansion could cause disease by loss of normal function of C9orf72 protein, RNA toxicity, and dipeptide‐repeat proteins aggregates. 3,4 Although the mechanisms for different phenotypes of C9orf72 HRE have not been well unveiled, the proteomic cerebrospinal fluid analyses and imaging studies provided potential biomarkers for C9orf72‐linked FTD and ALS. 5‐6 Previous studies showed the most common symptoms of C9orf72‐linked FTD were behavioral disinhibition and psychiatric disorders. 7‐9 Notably, 60% of C9orf72‐related FTD patients developed motor neuron disease symptoms during follow‐up. 9 C9orf72 HRE was the leading genetic cause of ALS and FTD in Caucasian populations, accounting for 21.7%‐47.0% in familial ALS, 13.8%‐48.1% in familial FTD, 4.1%‐21.1% in sporadic ALS, and 2.2%‐18.8% in sporadic FTD. 10,11 However, the C9orf72 HRE was rare in the Asian population, which could only explain around 0.4% ALS in Japan, 3.5% family ALS, and 0.5% sporadic ALS in Chinese populations. 12,13 The prevalence of C9orf72‐related FTD was not clear in China, which calls for a large‐scale multicenter study. The genetic investigation revealed more than 93 times repeat expansions (normal