RT Journal Article
SR Electronic
T1 Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP jnnp-2024-333403
DO 10.1136/jnnp-2024-333403
A1 Hobara, Takahiro
A1 Ando, Masahiro
A1 Higuchi, Yujiro
A1 Yuan, Jun-Hui
A1 Yoshimura, Akiko
A1 Kojima, Fumikazu
A1 Noguchi, Yutaka
A1 Takei, Jun
A1 Hiramatsu, Yu
A1 Nozuma, Satoshi
A1 Nakamura, Tomonori
A1 Adachi, Tadashi
A1 Toyooka, Keiko
A1 Yamashita, Toru
A1 Sakiyama, Yusuke
A1 Hashiguchi, Akihiro
A1 Matsuura, Eiji
A1 Okamoto, Yuji
A1 Takashima, Hiroshi
YR 2024
UL http://jnnp.bmj.com/content/early/2024/07/03/jnnp-2024-333403.abstract
AB Background The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions.Methods We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in LRP12, GIPC1 and RILPL1 genes was conducted using PCR and long-read sequencing technologies.Results We identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with LRP12-oculopharyngodistal myopathy (p<0.0001). Additionally, GIPC1 and RILPL1 repeat expansions were absent in our IPN cases.Conclusion We initially elucidate LRP12 repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.Data are available upon reasonable request. Data sets are not readily available due to ethical and privacy restrictions. Requests should be directed to the corresponding author.