Late-onset spastic ataxia phenotype in a patient with a homozygous DDHD2 mutation

Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias (ARHSPs) are clinically and genetically heterogeneous neurological disorders. Herein we describe Japanese siblings with a midlife-onset, slowly progressive type of cerebellar ataxia and spastic paraplegia, without intellectual disability. Using whole exome sequencing, we identified a homozygous missense mutation in DDHD2, whose mutations were recently identified as the cause of early-onset ARHSP with intellectual disability. Brain MRI of the patient showed a thin corpus callosum. Cerebral proton magnetic resonance spectroscopy revealed an abnormal lipid peak in the basal ganglia, which has been reported as the hallmark of DDHD2-related ARHSP (SPG 54). The mutation caused a marked reduction of phospholipase A(1) activity, supporting that this mutation is the cause of SPG54. Our cases indicate that the possibility of SPG54 should also be considered when patients show a combination of adult-onset spastic ataxia and a thin corpus callosum. Magnetic resonance spectroscopy may be helpful in the differential diagnosis of patients with spastic ataxia phenotype.ArticleSCIENTIFIC REPORTS. 4:7132 (2014)journal articl

〔研究ノート〕幼児の食生活に関する調査研究-朝食摂取を中心に-

The objective of the present study is to investigate approaches to dietary education at nursery schools by elucidating the actual dietary life of nursery school children and the dietary awareness of their parents. A questionnaire survey was conducted on a total of 1,049 parents of 4-year-old children attending public nursery schools in Ward S of Tokyo. Ninety seven point two percent of the responses were valid and the following results were obtained:1 A total of 97.4% of children ate breakfast every day, while 2.6% sometimes skipped it. Reasons for skipping it were lack of appetite(55.6%)and lack of time(27.8%).2 Regarding the people children ate breakfast with, the most common response was the mother(81.8%), and while few responded that their children ate alone(2.8%), 10.2% indicated that their children ate with other children only. Eating with other children only was associated with a low level of enjoyment, and the frequency of greetings before and after eating was also lower compared to when children ate with adults.3 As for the contents of breakfast, while 97.2% regularly ate a carbohydrate rich staple food, only 63.9% and 38.1% of children respectively ate a protein rich main dish such as fish or meat, and a side dish such as vegetables or seaweed every day. Breakfast contents were classified into five patterns, and the most common pattern was "Pattern 2: Staple food + one main or side dish"(33.9%), followed by the ideal combination of "Pattern 1: Staple food + main dish + side dish"(32.1%), and "Staple food only"(30.8%). Although few children skipped breakfast, these findings indicate the need to improve breakfast contents.4 "Pattern 1: Staple food + main dish + side dish" was more common among children who ate with adults compared to those who ate with other children only, children of parents who liked cooking compared to those of parents who disliked cooking, and among children who did not dislike any vegetables and children whose parents checked the lunch menu of their children\u27s nursery school every day.5 Intake of restaurant food, pre-cooked food, boxed meals, and convenience store food for breakfast was no more than once weekly. Intake of frozen food was slightly more frequent. These findings suggest that factors that positively affect breakfast intake among nursery school children include eating with adults overcoming any dislike of vegetables with the help of adults, and the parents coming to like cooking and developing a greater awareness regarding their children\u27s diet

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Parotid Oncocytoma as a Manifestation of Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disease characterized by skin fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces, and renal cancers. Oncocytomas are benign epithelial tumors that are also rare. Recently, there have been a few case reports of BHD with a parotid oncocytoma that appears to have a BHD phenotype. Here we document the eighth known case and describe the magnetic resonance imaging features of the parotid oncocytoma, which mimicked Warthin’s tumor. Radiologists should be aware of the association between these rare disorders