Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy.

This review aimed to determine the association between periodontal disease and stroke incidence by a meta-analysis of cohort studies. Cohort studies that evaluated the incidence of stroke (fatal or non-fatal, ischaemic or haemorrhagic) and baseline periodontal status and calculated relative risk values were included. The quality of the included studies was assessed using an evaluation grid. The analyses were conducted separately for three outcomes: periodontitis, gingivitis and loss of teeth. Adjusted values of relative risk or of hazard ratio were used to assess risk values in each study. Random effects meta-analyses were conducted when data could be pooled. From the 743 references retrieved, only nine cohort studies were suitable for inclusion in this review. Quality scores of the studies varied greatly. Three prospective studies, which used reliable indicators of periodontal disease, obtained the highest scores. Conversely, three studies that used a subjective evaluation of stroke incidence or diagnosed stroke without imaging obtained the lowest score. The results of the meta-analyses varied depending on the outcome considered and the type of stroke. The risk of stroke was significantly increased by the presence of periodontitis [relative risk 1.63 (1.25, 2.00)]. Tooth loss was also a risk factor for stroke [relative risk 1.39 (1.13, 1.65)]. The risk of stroke did not vary significantly with the presence of gingivitis. This review shows that periodontitis and tooth loss are associated with the occurrence of stroke.

This case-control study demonstrates that periodontal disease, especially markers such as BOP and bone loss, is independently associated with ischemic stroke.

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Hypopigmentation along Blaschko's lines is a hallmark of a poorly defined group of mosaic syndromes whose genetic causes are unknown. Here we show that postzygotic inactivating mutations of RHOA cause a neuroectodermal syndrome combining linear hypopigmentation, alopecia, apparently asymptomatic leukoencephalopathy, and facial, ocular, dental, and acral anomalies. Our findings pave the way towards elucidating the etiology of pigmentary mosaicism and highlight the role of RHOA in human development and disease.

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In the version of this article initially published, in Table 1, the final three numbers in the 'Trees' column were listed as '× 10 6 ' but should have been '× 10 3 '. In addition, the Acknowledgements had omitted support from the UK Biobank Resource, application number 12788. The errors have been corrected in the HTML and PDF versions of the article.