Analysis of NOTCH2NLC GGC repeat expansion in Taiwanese patients with amyotrophic lateral sclerosis

Jih, Kang-Yang; Chou, Yi‐Chieh; Tsai, Pei‐Chien; Liao, Yi‐Chu; Lee, Yi‐Chung

doi:10.1016/j.neurobiolaging.2021.07.011

Cited by 11 publications

(7 citation statements)

References 7 publications

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“…The proportion of mutated individuals might differ remarkably in different ethnic backgrounds, as previously www.nature.com/scientificreports/ observed for the mutation spectrum of ALS genes in the Chinese population 42 . However, a recent study failed to detect abnormal GGC repeats in NOTCH2NLC in a cohort of 304 unrelated Taiwan ALS patients, whereas an intermediate GGC repeat allele (46 repeats) was detected in 1 out of 637 control subjects 40 . Similarly, Tian and colleagues did not find expanded NOTCH2NLC alleles among 44 Chinese families affected by motor neuron disease, nor in 211 matched healthy controls 5 .…”

Section: Discussionmentioning

confidence: 92%

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NOTCH2NLC GGC repeats are not expanded in Italian amyotrophic lateral sclerosis patients

Manini

Gagliardi

Meneri

et al. 2023

Sci Rep

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Repeat expansions in genes other than C9orf72 and ATXN2 have been recently associated with Amyotrophic Lateral Sclerosis (ALS). Indeed, an abnormal number of GGC repeats in NOTCH2NLC has been recently reported in 0.7% of sporadic ALS patients from mainland China. This finding was not confirmed in an ALS cohort of subjects from Taiwan. As the involvement of expanded NOTCH2NLC alleles in ALS is debated, we addressed this point by evaluating NOTCH2NLC repeat expansions in an Italian cohort of ALS patients. A screening analysis of NOTCH2NLC GGC repeats was performed by repeat-primed polymerase chain reaction (RP-PCR) in a cohort of 385 probable/definite ALS Italian patients. Mean age at onset was 60.5 years (SD 13.7), and 60.9% were males. Sporadic cases were 357 (92.7%), and most patients had a spinal onset (71.8%). None of our patients showed the typical sawtooth tail pattern on RP-PCR, thus excluding abnormal repeat expansion in NOTCH2NLC. Overall, we suggest that NOTCH2NLC expanded alleles might be absent or at least extremely rare in ALS Italian patients. Further investigations in larger cohorts with different ethnic backgrounds are required to support the involvement of NOTCH2NLC in ALS.

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Section: Discussionmentioning

confidence: 92%

“…Based on these data, the authors suggested that GGC repeat expansions in NOTCH2NLC might be also associated with ALS [3][4][5]17,31 . However, different authors failed to detect similar expanded alleles in NOTCH2NLC in other Chinese and Taiwanese ALS cohorts 5,40 .…”

mentioning

confidence: 95%

NOTCH2NLC GGC repeats are not expanded in Italian amyotrophic lateral sclerosis patients

Manini

Gagliardi

Meneri

et al. 2023

Sci Rep

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“…The proportion of mutated individuals might differ remarkably in different ethnic backgrounds, as previously observed for the mutation spectrum of ALS genes in the Chinese population 11 . However, a recent study failed to detect abnormal GGC repeats in NOTCH2NLC in a cohort of 304 unrelated Taiwan ALS patients, whereas an intermediate GCC repeat allele (46 repeats) was detected in 1 out of 637 control subjects 12 . This is the rst assessment of the prevalence of GGC abnormal repeats in NOTCH2NLC in a European cohort of ALS patients.…”

Section: Discussionmentioning

confidence: 92%

NOTCH2NLC GCC repeats are not expanded in Italian Amyotrophic Lateral Sclerosis patients

Manini

Gagliardi

Meneri

et al. 2022

Preprint

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IntroductionRepeat expansions in genes other than C9orf72 and ATXN2 have been recently associated with Amyotrophic Lateral Sclerosis (ALS). Indeed, an abnormal number of GGC repeats in NOTCH2NLC has been recently reported in 0.7% of sporadic ALS patients from mainland China. This finding was not confirmed in an ALS cohort of subjects from Taiwan. As the involvement of expanded NOTCH2NLC alleles in ALS is debated, we addressed this point by evaluating NOTCH2NLC repeat expansions in an Italian cohort of ALS patients.MethodsA screening analysis of NOTCH2NLC GGC repeats was performed by repeat-primed polymerase chain reaction (RP-PCR) in a cohort of 350 probable/definite ALS Italian patients.ResultsMean age at onset was 60.7 years (SD 13.6), and 62.6% were males. Sporadic cases were 329 (94.0%), and most patients had a spinal onset (71.8%). None of our patients showed the typical sawtooth tail pattern on RP-PCR, thus excluding abnormal repeat expansion in NOTCH2NLC.DiscussionOverall, we suggest that NOTCH2NLC expanded alleles might be absent or at least extremely rare in ALS Italian patients. Further investigations in larger cohorts with different ethnic backgrounds are required to support the involvement of NOTCH2NLC in ALS.

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“…Muscle weakness tends to begin in the distal lower limbs and then move to the throat muscles and face. Recent studies have shown that many diseases with limb weakness, such as amyotrophic lateral sclerosis and oculopharyngodistal myopathy, are associated with NIID or NOTCH2NLC-related GGC repeat expansion disorders ( Ogasawara et al, 2020 ; Yuan et al, 2020 ; Jih et al, 2021 ; Sugiyama et al, 2021 ). A recent clinical study indicated that 62.7% of patients with NIID had muscle weakness ( Chen et al, 2020a ).…”

Section: Clinical Symptoms Of Neuronal Intranuclear Inclusion Diseasementioning

confidence: 99%

Clinical and mechanism advances of neuronal intranuclear inclusion disease

Liu

et al. 2022

Front. Aging Neurosci.

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Due to the high clinical heterogeneity of neuronal intranuclear inclusion disease (NIID), it is easy to misdiagnose this condition and is considered to be a rare progressive neurodegenerative disease. More evidence demonstrates that NIID involves not only the central nervous system but also multiple systems of the body and shows a variety of symptoms, which makes a clinical diagnosis of NIID more difficult. This review summarizes the clinical symptoms in different systems and demonstrates that NIID is a multiple-system intranuclear inclusion disease. In addition, the core triad symptoms in the central nervous system, such as dementia, parkinsonism, and psychiatric symptoms, are proposed as an important clue for the clinical diagnosis of NIID. Recent studies have demonstrated that expanded GGC repeats in the 5′-untranslated region of the NOTCH2NLC gene are the cause of NIID. The genetic advances and possible underlying mechanisms of NIID (expanded GGC repeat-induced DNA damage, RNA toxicity, and polyglycine-NOTCH2NLC protein toxicity) are briefly summarized in this review. Interestingly, inflammatory cell infiltration and inflammation were observed in the affected tissues of patients with NIID. As a downstream pathological process of NIID, inflammation could be a therapeutic target for NIID.

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Analysis of NOTCH2NLC GGC repeat expansion in Taiwanese patients with amyotrophic lateral sclerosis

Cited by 11 publications

References 7 publications

NOTCH2NLC GGC repeats are not expanded in Italian amyotrophic lateral sclerosis patients

NOTCH2NLC GGC repeats are not expanded in Italian amyotrophic lateral sclerosis patients

NOTCH2NLC GCC repeats are not expanded in Italian Amyotrophic Lateral Sclerosis patients

Clinical and mechanism advances of neuronal intranuclear inclusion disease

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