GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy

Autor: Li Cao, Jiaxi Yu, Xing-Hua Luan, Yun Yuan, Lingchao Meng, Zhaoxia Wang, Pidong Li, Daojun Hong, Xiao-Rong Wu, Jianwen Deng, Zhi-rong Jia, He Lv, Wei Zhang, Meng Yu, Wei Liang, Jing Liu, Min Zhu, Sheng Yao, Xin Shi, Qiang Gang, Binbin Zhou
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
Weakness
Pathology
medicine.medical_specialty
Candidate gene
Intranuclear Inclusion Bodies
Central nervous system
Nerve Tissue Proteins
Neurosciences. Biological psychiatry. Neuropsychiatry
03 medical and health sciences
0302 clinical medicine
Exome Sequencing
medicine
Humans
Myopathy
RC346-429
Pathological
Research Articles
business.industry
General Neuroscience
Middle Aged
Spinal cord
Phenotype
Pedigree
Distal Myopathies
030104 developmental biology
medicine.anatomical_structure
Intercellular Signaling Peptides and Proteins
Female
Neurology (clinical)
Neurology. Diseases of the nervous system
medicine.symptom
Hereditary Sensory and Motor Neuropathy
Trinucleotide Repeat Expansion
Trinucleotide repeat expansion
business
030217 neurology & neurosurgery
Research Article
RC321-571
Zdroj: Annals of Clinical and Translational Neurology, Vol 8, Iss 6, Pp 1330-1342 (2021)
Annals of Clinical and Translational Neurology
ISSN: 2328-9503
Popis: Background The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC. Methods Whole‐exome sequencing (WES) and long‐read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied. Results We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy. Interpretation These phenotypes enrich the class of features associated with NOTCH2NLC‐related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.
Databáze: OpenAIRE
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