An NEFH founder mutation causes broad phenotypic spectrum in multiple Japanese families.

BACKGROUND AND AIMS: Mutations in neurofilament genes have been linked to several neuromuscular disorders. The neurofilament heavy (NEFH) gene was identified as the causative gene of Charcot-Marie-Tooth disease type 2CC (CMT2CC) in 2016, with a toxic gain of function mechanism caused by the translation and aggregation of cryptic amyloidogenic element (CAE) in the 3' untranslated region (UTR). But the NEFH-related clinical and genetic spectrums are still unclear in Japan. METHODS: We analyzed all variants in the NEFH gene from our in-house whole-exome sequencing data, established from Japanese nationwide patients with neuromuscular disorders, including Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA). RESULTS: We identified a c.3017dup (p.Pro1007Alafs*56) variant in NEFH from three families clinically diagnosed with CMT, and one family with SMA. In addition to the patients presented with typical peripheral neuropathies, pyramidal signs were observed from one CMT patient. Whereas the SMA patients showed severe characteristic weakness of triceps brachii and quadriceps femoris. All of these four families reside in Kagoshima Prefecture of Japan, and a following haplotype analysis strongly suggests a founder effect. INTERPRETATION: This is the original report referring to a founder mutation in NEFH. The clinical diversity in our study, comprising CMT, with or without pyramidal signs, and SMA, suggest an extensive involvement of peripheral nerve, anterior horn cells, or both. Our findings broaden the phenotypic spectrum of NEFH-related disorders.

Diagnosis of a C3 segmental type of vertebral artery by magnetic resonance angiography: report of two cases.

We report two cases in which the vertebral artery (VA) entered the spinal canal via the intervertebral foramen at the C2-C3 disc level, an extremely rare variation regarded as a C3 segmental type of VA, that we diagnosed by magnetic resonance angiography. The C2 segmental type of VA, in which the VA enters the spinal canal via the C1-C2 intervertebral space, is relatively common. It is important to identify these variations before surgery of the craniovertebral junction or interventional procedures to prevent complications.

[A case of Reye's-like syndrome due to suspected Bordetella pertussis infection in an adult].

We report a rare case of Reye's-like syndrome associated with suspected pertussis infection. A 26-year-old woman admitted comatose and found in laboratory studies to have acute liver dysfunction, severe hypoglycemia and prolonged prothrombin time, was diagnosed with clinical Reye's-like syndrome due to aspirin use. Her child was probably infected with pertussis, which she contracted and which, in turn, triggered Reye's-like syndrome.

Expression of the heparin-binding growth factor midkine in the cerebrospinal fluid of patients with neurological disorders.

OBJECTIVE: This study was to clarify the roles of midkine (MK) in the brain. METHODS: We determined cerebrospinal fluid MK levels in patients with neurological disorders by enzyme-linked immunoassay and immunostained autopsied brain samples in patients with meningitis. RESULTS: MK levels were 0.37+/-0.21 ng/ml in controls (n=46, mean +/- S.D.), 0.67+/-0.19 ng/ml in patients with cerebral infarction (n=8), 1.78+/-1.32 ng/ml in patients with meningitis (n=25; ANOVA and post-hoc Fisher's PLSD test, p<0.0001), 0.31+/-0.25 ng/ml in patients with human T-lymphotrophic virus type I-associated myelopathy/tropical spastic paraparesis (n=29), and 0.42+/-0.17 ng/ml in patients with amyotrophic lateral sclerosis (n=8). The regression equations were Y=0.005X+0.498 (Y, CSF MK level; X, cell number) and Y=0.007X+0.326 (Y, MK level; X, protein level) for all CSF samples. Autopsy brain samples from patients with meningitis expressed MK weakly in mononuclear cells on immunohistochemical examination. Western blot and polymerase chain reaction analyses showed that leukocytes were MK positive. CSF MK levels were not high in patients with cerebral infarction but were increased in patients with meningitis. CSF MK levels were high in normal controls, compared to those of other cytokines. MK was expressed in choroid plexus of normal brain and released there. CONCLUSION: Our findings suggested that MK may maintain normal adult brain as a neurotrophic factor, and that MK may be released from leucocytes in brain of patients with meningitis as an immunological mediator.