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1. Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort

   https://doi.org/10.1111/epi.16288  

   Encinas, Alejandra C. ; Moore, Ida ; Watkins, Joseph C. ; Hammer, Michael F. ( July 2019 , Epilepsia)

   To characterize a cohort of patients withSCN8A‐related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills.

   We analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children withSCN8Avariants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the DenverIIitems. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression.

   The 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant inSCN8Aand those with an additional variant reported in a gene other thanSCN8A, as well as between patients with different patterns of regression before and at seizure onset.

   This is the first study of anSCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children withSCN8A‐related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures forSCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.

    

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2. Binge‐eating disorder with and without lifetime anorexia nervosa: A comparison of sociodemographic and clinical features

   https://doi.org/10.1002/eat.23858  

   Pawar, Pratiksha S. ; Thornton, Laura M. ; Flatt, Rachael E. ; Sanzari, Christina M. ; Carrino, Emily A. ; Tregarthen, Jenna P. ; Argue, Stuart ; Bulik, Cynthia M. ; Watson, Hunna J. ( November 2022 , International Journal of Eating Disorders)

   To compare individuals who have experienced binge‐eating disorder (BED) and anorexia nervosa (AN) (BED AN+) to those who have experienced BED and not AN (BED AN–).

   Participants (N = 898) met criteria for lifetime BED and reported current binge eating. Approximately 14% had a lifetime diagnosis of AN. Analyses compared BED AN+ and BED AN– on sociodemographic variables and clinical history.

   The presence of lifetimeANwas associated with more severe eating disorder symptoms, including earlier onset, more frequent, more chronic, and more types of eating disorder behaviors over the lifetime, as well as a higher lifetime prevalence of bulimia nervosa (BN). Participants with lifetimeANreported being more likely to have received treatments forBEDorBN, had significantly lower minimum, current, and maximumBMIs, had more severe general anxiety, and were significantly more likely to be younger and female. In the full sample, the lifetime prevalence of unhealthy weight control behaviors was high and treatment utilization was low, despite an average 15‐year history since symptom onset. Gastrointestinal disorders and comorbid anxiety, depression, and attention‐deficit/hyperactivity disorder symptoms were prevalent.

   Individuals fared poorly on a wide array of domains, yet those with lifetimeANfared considerably more poorly. All patients withBEDshould be screened for mental health and gastrointestinal comorbidities and offered referral and treatment options.

   Individuals experiencing binge‐eating disorder have severe symptomology, but those who have experienced binge‐eating disorder and anorexia nervosa fare even more poorly. Our study emphasizes that patients with binge‐eating disorder would benefit from being screened for mental health and gastrointestinal comorbidities, and clinicians should consider history of unhealthy weight control behaviors to inform treatment and relapse prevention.

    

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3. The interictal mesial temporal lobe epilepsy network

   https://doi.org/10.1111/epi.13959  

   Karunakaran, Suganya ; Rollo, Matthew J. ; Kim, Kamin ; Johnson, Jessica A. ; Kalamangalam, Giridhar P. ; Aazhang, Behnaam ; Tandon, Nitin ( December 2017 , Epilepsia)

   Identification of patient‐specific epileptogenic networks is critical to designing successful treatment strategies. Multiple noninvasive methods have been used to characterize epileptogenic networks. However, these methods lack the spatiotemporal resolution to allow precise localization of epileptiform activity. We used intracranial recordings, at much higher spatiotemporal resolution, across a cohort of patients with mesial temporal lobe epilepsy (MTLE) to delineate features common to their epileptogenic networks. We used interictal rather than seizure data because interictal spikes occur more frequently, providing us greater power for analyzing variances in the network.

   Intracranial recordings from 10 medically refractoryMTLEpatients were analyzed. In each patient, hour‐long recordings were selected for having frequent interictal discharges and no ictal events. For all possible pairs of electrodes, conditional probability of the occurrence of interictal spikes within a 150‐millisecond bin was computed. These probabilities were used to construct a weighted graph between all electrodes, and the node degree was estimated. To assess the relationship of the highly connected regions in this network to the clinically identified seizure network, logistic regression was used to model the regions that were surgically resected using weighted node degree and number of spikes in each channel as factors. Lastly, the conditional spike probability was normalized and averaged across patients to visualize theMTLEnetwork at group level.

   We generated the first graph of connectivity across a cohort ofMTLEpatients using interictal activity. The most consistent connections were hippocampus to amygdala, anterior fusiform cortex to hippocampus, and parahippocampal gyrus projections to amygdala. Additionally, the weighted node degree and number of spikes modeled the brain regions identified as seizure networks by clinicians.

   Apart from identifying interictal measures that can model patient‐specific epileptogenic networks, we also produce a group map of network connectivity from a cohort ofMTLEpatients.

    

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4. A Tunisian family with a novel mutation in the gene CYP4F22 for lamellar ichthyosis and co‐occurrence of hearing loss in a child due to mutation in the SLC26A4 gene

   https://doi.org/10.1111/ijd.14452  

   Sayeb, Marwa ; Riahi, Zied ; Laroussi, Nadia ; Bonnet, Crystel ; Romdhane, Lilia ; Mkaouar, Rahma ; Zaouak, Anissa ; Marrakchi, Jihene ; Abdessalem, Ghaith ; Messaoud, Olfa ; et al ( April 2019 , International Journal of Dermatology)

   Co‐occurrence of two genetic diseases is challenging for accurate diagnosis and genetic counseling. The recent availability of whole exome sequencing (WES) has dramatically improved the molecular diagnosis of rare genetic diseases in particular in consanguineous populations.

   We report here on a consanguineous family from Southern Tunisia including three members affected with congenital ichthyosis. The index case had a hearing loss (HL) and ichthyosis and was primarily suspected as suffering from keratitis‐ichthyosis‐deafness (KID) syndrome.WESwas performed for the index case, and all members of the nuclear family were sequenced (Sanger method).

   TheWESapproach allowed the identification of two strong candidate variants in two different genes; a missense mutation c.1334T>G (p.Leu445Trp) in exon 11 ofSLC26A4gene, associated with isolatedHLand a novel missense mutation c.728G>T (p.Arg243Leu) in exon 8 ofCYP4F22gene likely responsible for ichthyosis. These two mutations were predicted to be pathogenic by three pathogenicity prediction softwares (Scale‐Invariant Feature Transform [SIFT], Polymorphism Phenotyping [PolyPhen], Mutation Taster) to underlie theHLand ichthyosis, respectively.

   The present study raises awareness about the importance of familial history for accurate diagnosis of syndromic genetic diseases and differential diagnosis with co‐occurrence of two distinct clinical entities. In addition, in countries with limited resources,WESsequencing for a single individual provides a cost effective tool for molecular diagnosis confirmation and genetic counseling.

    

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5. Nuclear‐encoded sigma factor 6 ( SIG 6) is involved in the block of greening response in Arabidopsis thaliana

   https://doi.org/10.1002/ajb2.1423  

   Alameldin, Hussien F. ; Oh, Sookyung ; Hernandez, Alexandra P. ; Montgomery, Beronda L. ( January 2020 , American Journal of Botany)

   Light is critical in the ability of plants to accumulate chlorophyll. When exposed to far‐red (FR) light and then grown in white light in the absence of sucrose, wild‐type seedlings fail to green in a response known as theFRblock of greening (BOG). This response is controlled by phytochrome A through repression of protochlorophyllide reductase‐encoding (POR) genes byFRlight coupled with irreversible plastid damage. Sigma (SIG) factors are nuclear‐encoded proteins that contribute to plant greening and plastid development through regulating gene transcription in chloroplasts and impacting retrograde signaling from the plastid to nucleus.SIGs are regulated by phytochromes, and the expression of someSIGfactors is reduced in phytochrome mutant lines, including phyA. Given the association of phyA with theFR BOGand its regulation ofSIGfactors, we investigated the potential regulatory role ofSIGfactors in theFR BOGresponse.

   We examinedFR BOGresponses insigmutants, phytochrome‐deficient lines, and mutant lines for several phy‐associated factors. We quantified chlorophyll levels and examined expression of keyBOG‐associated genes.

   Among sixsigmutants, only thesig6 mutant significantly accumulated chlorophyll afterFR BOGtreatment, similar to thephyAmutant.SIG6 appears to control protochlorophyllide accumulation by contributing to the regulation of tetrapyrrole biosynthesis associated with glutamyl‐tRNAreductase (HEMA1) function, select phytochrome‐interacting factor genes (PIF4andPIF6), andPENTA1, which regulatesPORAmRNAtranslation afterFRexposure.

   Regulation ofSIG6plays a significant role in plant responses toFRexposure during theBOGresponse.

    

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