Unilateral internal carotid artery absence in trisomy 18.

BACKGROUND: Internal carotid artery (ICA) absence (agenesis or aplasia) is a rare congenital anomaly that is usually asymptomatic and found coincidentally. There has been no report showing a specific chromosomal abnormality causes ICA absence. CASE REPORTS: MR angiography in a Japanese male infant with trisomy 18 revealed left ICA absence with the left middle cerebral artery (MCA) and anterior cerebral artery (ACA) supplied from the ipsilateral posterior communicating artery and anterior communicating artery (ACoA), respectively, type A in Lie's classification. Another Japanese male infant with trisomy 18 showed right ICA absence with the right ACA and MCA supplied from the ACoA, that is, type B in Lie's classification. CONCLUSION: There have been no pathological or radiological reports of ICA absence in trisomy 18, however, it may be underestimated because the anomaly usually causes no clinical symptoms. It is necessary to evaluate further patients to clarify whether or not unilateral ICA absence is a characteristic congenital malformation.

Acute Flaccid Myelitis With Neuroradiological Finding of Brachial Plexus Swelling.

BACKGROUND: Acute flaccid myelitis is a recently defined clinically distinct syndrome of polio-like acute flaccid paralysis. Acute flaccid myelitis cases show characteristic neuroradiological features of longitudinal spinal cord lesions with predominant gray matter involvement. Current evidence suggests injury to the anterior horn neurons as the underlying mechanism. METHODS: We describe three patients with acute flaccid myelitis who developed flaccid upper limb weakness with diminished deep tendon reflexes after prodromal fever. Spinal magnetic resonance imaging (MRI) (axial and sagittal T1- and T2-weighted sequences) and brachial plexus MRI (coronal short tau inversion recovery sequence) at the acute stage were performed. RESULTS: Spinal MRI showed extensive longitudinal lesion in the spinal cord with predominant gray matter involvement. We were able to demonstrate concurrent swelling and hyperintensity in the brachial plexus in all the three patients at the acute stage. CONCLUSION: The coexisting signal intensities suggest an extension of acute flaccid myelitis pathology to the brachial plexus, highlighting the possible peripheral nerve involvement in acute flaccid myelitis.

Single-fiber electromyography-based diagnosis of CACNA1A mutation in children: A potential role of the electrodiagnosis in the era of whole exome sequencing.

INTRODUCTION: A loss-of-function mutation in CACNA1A, which encodes P/Q-type Ca channels, causes various diseases. As most of the Ca channels at neuromuscular junctions are of the P/Q type, patients with loss-of-function CACNA1A mutations exhibit disturbed neuromuscular transmission. The associated jitters and blocking in such patients can be detected by single-fiber electromyography (SFEMG). CASES: We report two cases with different phenotypes, which were predicted to harbor loss-of-function mutations of CACNA1A, by using axonal stimulation SFEMG. One case involved a 2-year-old boy with episodic ataxia type 2. The other case involved a 7-year-old girl diagnosed with epileptic encephalopathy. SFEMG results revealed jitters and blocking in both cases. Moreover, whole exome sequencing (WES) revealed a heterozygous CACNA1A mutation, c.5251C>T, p.Arg1751Trp, in the former case and a novel de novo CACNA1A mutation, c.2122G>A, p.Val708Met, in the latter. CONCLUSIONS: Our cases indicate that SFEMG is a potentially useful diagnostic tool for patients with CACNA1A mutation, especially in pediatric cases where trio analysis is difficult or novel mutations are present.

Epileptic apnea in a patient with inherited glycosylphosphatidylinositol anchor deficiency and PIGT mutations.

We report an 11-month-old boy with acetazolamide-responsive epileptic apnea and inherited glycosylphosphatidylinositol (GPI)-anchor deficiency who presented with decreased serum alkaline phosphatase associated with compound PIGT mutations. The patient exhibited congenital anomalies, severe intellectual disability, and seizures, including epileptic apnea with epileptiform discharges from bilateral temporal areas. Brain magnetic resonance imaging revealed delayed myelination and progressive atrophy of the brainstem, cerebellum, and cerebrum. Whole-exome sequencing revealed compound heterozygous mutations in PIGT (c.250G>T, p.Glu84X and c.1096G>T, p.Gly366Trp), which encodes a subunit of the GPI transamidase complex. Flow cytometry revealed decreased expression of CD16 (a GPI anchor protein) on granulocytes, supporting the putative pathogenicity of the mutations. Phenobarbital, clonazepam, and potassium bromide decreased the frequency of tonic seizure and acetazolamide decreased epileptic apnea. To our knowledge, this is the first reported case of intractable seizures accompanied by epileptic apnea associated with GPI anchor deficiency and a compound PIGT mutation.

Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.

Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic syndromes characterized by migrating polymorphous focal seizures. Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K(+)-Cl(-) co-transporter KCC2) mutations in two families: c.279 + 1G > C causing skipping of exon 3 in the transcript (p.E50_Q93del) and c.572 C >T (p.A191V) in individuals 1 and 2, and c.967T > C (p.S323P) and c.1243 A > G (p.M415V) in individual 3. Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy. Gramicidin-perforated patch-clamp analysis demonstrated strongly suppressed Cl(-) extrusion function of E50_Q93del and M415V mutants, with mildly impaired function of A191V and S323P mutants. Cell surface expression levels of these KCC2 mutants were similar to wildtype KCC2. Heterologous expression of two KCC2 mutants, mimicking the patient status, produced a significantly greater intracellular Cl(-) level than with wildtype KCC2, but less than without KCC2. These data clearly demonstrated that partially disrupted neuronal Cl(-) extrusion, mediated by two types of differentially impaired KCC2 mutant in an individual, causes EIMFS.

A mild case of giant axonal neuropathy without central nervous system manifestation.

An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This case is important since it can aid to identify atypical and milder clinical courses of GAN. This report widens the mild GAN clinical spectrum, alerting physicians for correct diagnosis.

Hypoyelination in I-cell disease; MRI, MR spectroscopy and neuropathological correlation.

MRI of a female patient with genetically diagnosed I-cell disease at 2weeks, 4 and 8months revealed delayed myelination or hypomyelination with decreased choline on MR spectroscopy. Brain autopsy was performed 2h after death at 14-month-old. Immunoreactivities for myelin basic protein and proteolipid proteins, markers for mature myelin sheath, were reduced in the myelinated fibers and oligodendrocytes in the white matter, indicating the hypomyelination in the central nervous system. I-Cell disease should be added to the list of delayed or hypomyelination conditions, and this neuroimaging finding could be a key for differentiating I-cell disease from the clinically similar disorder of Hurler syndrome characterized by perivascular lacunation.

Sequence analysis of the genome of an oil-bearing tree, Jatropha curcas L.

The whole genome of Jatropha curcas was sequenced, using a combination of the conventional Sanger method and new-generation multiplex sequencing methods. Total length of the non-redundant sequences thus obtained was 285 858 490 bp consisting of 120 586 contigs and 29 831 singlets. They accounted for ~95% of the gene-containing regions with the average G + C content was 34.3%. A total of 40 929 complete and partial structures of protein encoding genes have been deduced. Comparison with genes of other plant species indicated that 1529 (4%) of the putative protein-encoding genes are specific to the Euphorbiaceae family. A high degree of microsynteny was observed with the genome of castor bean and, to a lesser extent, with those of soybean and Arabidopsis thaliana. In parallel with genome sequencing, cDNAs derived from leaf and callus tissues were subjected to pyrosequencing, and a total of 21 225 unigene data have been generated. Polymorphism analysis using microsatellite markers developed from the genomic sequence data obtained was performed with 12 J. curcas lines collected from various parts of the world to estimate their genetic diversity. The genomic sequence and accompanying information presented here are expected to serve as valuable resources for the acceleration of fundamental and applied research with J. curcas, especially in the fields of environment-related research such as biofuel production. Further information on the genomic sequences and DNA markers is available at http://www.kazusa.or.jp/jatropha/.