Identification of a novel splice-site WWOX variant with paternal uniparental isodisomy in a patient with infantile epileptic encephalopathy.

WOREE syndrome is an early infantile epileptic encephalopathy characterized by drug-resistant seizures and severe psychomotor developmental delays. We report a case of a WWOX splice-site mutation with uniparental isodisomy. A 1-year and 7-month-old girl presented with nystagmus and epileptic seizures from early infancy, with no fixation or pursuit of vision. Physical examination revealed small deformities, such as swelling of both cheeks, folded fingers, rocking feet, and scoliosis. Brain imaging revealed slight hypoplasia of the cerebrum. Electroencephalogram showed focal paroxysmal discharges during the interictal phase of seizures. Vitamin B6 and zonisamide were administered for early infantile epileptic encephalopathy; however, the seizures were not relieved. Despite altering the type and dosage of antiepileptic drugs and ACTH therapy, the seizures were intractable. Whole-exome analysis revealed the homozygosity of WWOX(NM_016373.4):c.516+1G>A. The WWOX mRNA sequencing using peripheral blood RNA confirmed that exon 5 was homozygously deleted. Based on these results, the patient was diagnosed with WOREE syndrome at 5 months. The WWOX variant found in this study is novel and has never been reported before. WOREE syndrome being extremely rare, further case series and analyses of its pathophysiology are warranted.

An exceptionally well-preserved monodominant fossil forest of Wataria from the lower Miocene of Japan.

Byttneriophyllum tiliifolium is a leaf fossil-species of the family Malvaceae that was distributed widely throughout Eurasia from the Miocene to the Pliocene. An affinity to some Malvadendrina subfamilies has been suggested for Byttneriophyllum-bearing plants, but remains to be clarified due to insufficient information on other organs. Here, we report an exceptional lower Miocene fossil locality in Japan where a monodominant forest of the wood fossil-species Wataria parvipora flourished. Notably, the forest floor was covered by a bed consisting almost exclusively of B. tiliifolium. We observed occurrence modes of B. tiliifolium in this bed that confirmed that these leaves were deposited parautochthonously. These observations imply a biological connection between B. tiliifolium and W. parvipora. The wood and leaf characters together might narrow the affinity of Byttneriophyllum-bearing plants down to Helicterioideae within the Malvadendrina, although it is also possible that Byttneriophyllum-bearing plants constitutes an extinct lineage which is characterized by a combination of morphological traits found in several extant lineages. Our results suggest that Byttneriophyllum-bearing plants started to inhabit swamps no later than the end of the early Miocene when the global temperature was getting warmer.

Mutation of the imprinted gene OsEMF2a induces autonomous endosperm development and delayed cellularization in rice.

In angiosperms, endosperm development comprises a series of developmental transitions controlled by genetic and epigenetic mechanisms that are initiated after double fertilization. Polycomb repressive complex 2 (PRC2) is a key component of these mechanisms that mediate histone H3 lysine 27 trimethylation (H3K27me3); the action of PRC2 is well described in Arabidopsis thaliana but remains uncertain in cereals. In this study, we demonstrate that mutation of the rice (Oryza sativa) gene EMBRYONIC FLOWER2a (OsEMF2a), encoding a zinc-finger containing component of PRC2, causes an autonomous endosperm phenotype involving proliferation of the central cell nuclei with separate cytoplasmic domains, even in the absence of fertilization. Detailed cytological and transcriptomic analyses revealed that the autonomous endosperm can produce storage compounds, starch granules, and protein bodies specific to the endosperm. These events have not been reported in Arabidopsis. After fertilization, we observed an abnormally delayed developmental transition in the endosperm. Transcriptome and H3K27me3 ChIP-seq analyses using endosperm from the emf2a mutant identified downstream targets of PRC2. These included >100 transcription factor genes such as type-I MADS-box genes, which are likely required for endosperm development. Our results demonstrate that OsEMF2a-containing PRC2 controls endosperm developmental programs before and after fertilization.