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Abstract Background Both fragile X-associated tremor/ataxia syndrome (FXTAS) and late-onset neuronal intranuclear inclusion disease (NIID) show CGG/GGC trinucleotide repeat expansions. Differentiating these diseases are difficult because of the similarity in their clinical and radiological features. It is unclear that skin biopsy can distinguish NIID from FXTAS. We performed a skin biopsy in an FXTAS case with cognitive dysfunction and peripheral neuropathy without tremor, which was initially suspected to be NIID. Case presentation The patient underwent neurological assessment and examinations, including laboratory tests, electrophysiologic test, imaging, skin biopsy, and genetic test. A brain MRI showed hyperintensity lesions along the corticomedullary junction on diffusion-weighted imaging (DWI) in addition to middle cerebellar peduncle sign (MCP sign). We suspected NIID from the clinical picture and the radiological findings, and performed a skin biopsy. The skin biopsy specimen showed ubiquitin- and p62-positive intranuclear inclusions, suggesting NIID. However, a genetic analysis for NIID using repeat-primed polymerase chain reaction (RP-PCR) revealed no expansion detected in the Notch 2 N-terminal like C (NOTCH2NLC) gene. We then performed genetic analysis for FXTAS using RP-PCR, which revealed a repeat CGG/GGC expansion in the FMRP translational regulator 1 (FMR1) gene. The number of repeats was 83. We finally diagnosed the patient with FXTAS rather than NIID. Conclusions For the differential diagnosis of FXTAS and NIID, a skin biopsy alone is insufficient; instead, genetic analysis, is essential. Further investigations in additional cases based on genetic analysis are needed to elucidate the clinical and pathological differences between FXTAS and NIID.

Abstract Background The coexistence of distinct neurodegenerative diseases in single cases has recently attracted greater attention. The phenotypic co-occurrence of progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) has been documented in several cases. That said, the clinicopathological comorbidity of these two diseases has not been demonstrated. Case presentation A 77-year-old man presented with gait disturbance for 2 years, consistent with PSP with progressive gait freezing. At 79 years old, he developed muscle weakness compatible with ALS. The disease duration was 5 years after the onset of PSP and 5 months after the onset of ALS. Neuropathological findings demonstrated the coexistence of PSP and ALS. Immunohistochemical examination confirmed 4-repeat tauopathy, including globose-type neurofibrillary tangles, tufted astrocytes, and oligodendroglial coiled bodies as well as TAR DNA-binding protein 43 kDa pathology in association with upper and lower motor neuron degeneration. Immunoblotting showed hyperphosphorylated full-length 4-repeat tau bands (64 and 68 kDa) and C-terminal fragments (33 kDa), supporting the diagnosis of PSP and excluding other parkinsonian disorders, such as corticobasal degeneration. Genetic studies showed no abnormalities in genes currently known to be related to ALS or PSP. Conclusions Our case demonstrates the clinicopathological comorbidity of PSP and ALS in a sporadic patient. The possibility of multiple proteinopathies should be considered when distinct symptoms develop during the disease course.

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Background Spinocerebellar ataxias (SCAs) are heterogeneous diseases characterized by progressive cerebellar ataxia associated with dysarthria, oculomotor abnormalities, and mental impairment. To identify the causative gene, we performed exome sequencing on a Japanese patient clinically diagnosed with recessive SCA. Method The patient is a 37-year-old Japanese woman with consanguineous parents. The head magnetic resonance imaging (MRI) showed cerebellar atrophy and T1 low/T2 high intensity at the bilateral inferior olives. Single-nucleotide polymorphism (SNP) genotyping and nextgeneration sequencing were performed, and the variants obtained were filtered and prioritized. Results After these manipulations, we identified a homozygous nonsense mutation of the TTC19 gene (p.Q277"). TTC19 has been reported to be a causative gene of a neurodegenerative disease in Italian and Portuguese families and to be involved in the pathogenesis of mitochondrial respiratory chain complex III (cIII) deficiency. This report is the first description of a TTC19 mutation in an Asian population. Clinical symptoms and neuroimaging are consistent with previous reports. The head MRI already showed abnormal features four years before her blood lactate and pyruvate levels were elevated. Conclusions We should consider the genetic analysis of TTC19 when we observe such characteristic MRI abnormalities. Genes associated with mitochondrial function cause many types of SCAs; the mutation we identified should help to elucidate the pathology of these disorders. [ABSTRACT FROM AUTHOR]