12 research outputs found

    Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes

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    Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.Peer reviewe

    Characteristics of the members of the study group.

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    <p>In June 2008, Lekoko was first introduced to Oudiki, Kouki and Tiya, who was a few months old and hand-fed daily. Eventually, Bumbi joined the group in October 2009, four months before the beginning of this study.</p><p>Characteristics of the members of the study group.</p

    Social networks of (a) play interactions between gorillas and of (b) close proximity between individuals and their nearest neighbour, for each of the three behavioural ecological periods.

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    <p>The social networks are scaled for comparisons between periods. Scales of (a) and (b) are not comparable. Period 1 of high frugivory and play comprises February and March, period 2 of Dialium fruits consumption stretches from April to August and period 3 of high folivory comprises September and October 2010. BU: Bumbi (dead in period 3); KU: Kouki; LK: Lekoko; OD: Oudiki; TY: Tiya Square vertices: females (BU, KU, LK, TY); triangular vertices: male (OD) Pink vertices: captive-born gorillas (KU, OD, TY); green vertices: wild-born gorillas (BU, LK)</p

    Behavioural Ecology and Group Cohesion of Juvenile Western Lowland Gorillas (<i>Gorilla g</i>. <i>gorilla</i>) during Rehabilitation in the Batéké Plateaux National Park, Gabon

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    <div><p>Rehabilitation of animals followed by reintroduction into the wild can benefit conservation by supplementing depleted wild populations or reintroducing a species in an area where it has been extirpated or become extinct. The western lowland gorilla (WLG, <i>Gorilla g. gorilla</i>) is persistently poached; infants are often illegally traded and used as pets. Some are confiscated and rehabilitated, then kept in sanctuaries or reintroduced into the wild. Prior to reintroduction, the ability of the orphans to survive independently in their environment needs to be assessed. Here, we performed a multivariate analysis, including diet composition, activity-budget, and pattern of strata using of a group of five juvenile WLG in the process of rehabilitation and distinguished three sub-periods of ecological significance: the high furgivory period, the <i>Dialium</i> fruits consumption period, and the high folivory period. The consequences of these variations on their well-being (play behaviour) and the group cohesion (spatial proximity and social interactions) were examined. Like wild WLGs, diets shifted seasonally from frugivorous to folivorous, while the same staple foods were consumed and large amounts of <i>Dialium</i> fruits were seasonally gathered high in trees. When succulent fruit intake was the highest, thus providing high energy from sugar, juveniles spent less time feeding, more time playing and group cohesion was the highest. Conversely, the cohesion decreased with increasing folivory, individuals spent more time feeding and less time playing together. Nonetheless, the group cohesion also decreased after the death of one highly social, wild-born orphan. This may underscore the importance of skilled individuals in the cohesion and well-being of the entire group and, ultimately, to rehabilitation success. This study evaluates the rehabilitation success with regards to the methods used and highlights the need to consider a set of individual and environmental factors for enhancing rehabilitation while preserving the local biodiversity and individual well-being.</p></div

    Location of the study site (left) and map area of the study group (right).

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    <p>Home range of the focal group for the entire study (February 2010 to October 2010) is presented in yellow (95% Minimum convex polygons) and in red (95% kernel home range) (using Garmin GPSMAP 60CSx and Biotas Version 2.0a, Ecological Software Solutions). The division of the study group home range in two areas resulted from the late use of the south-east area in September and October, after Bumbi death.</p

    Procustean analysis between the two first axes (SynVar1; SynVar2) of the reference structure (i.e. compromise) obtained from the multiple co-inertia analysis of the three behavioural ecological tables and the play behaviours.

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    <p>Procustean analysis between the two first axes (SynVar1; SynVar2) of the reference structure (i.e. compromise) obtained from the multiple co-inertia analysis of the three behavioural ecological tables and the play behaviours.</p

    Results of the Spearman’s product correlation tests between play variables and ecological variables.

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    <p>All tests are significant.</p><p>Results of the Spearman’s product correlation tests between play variables and ecological variables.</p

    Results of the comparisons between periods (Wilcoxon tests).

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    <p>All not significant tests are noted "ns"; all others are significant.</p><p>Results of the comparisons between periods (Wilcoxon tests).</p

    Multiple Co-inertia Analysis (MCOA): (3a) projection of the variables and (3b) projection of the months on the two first axis.

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    <p>In 5a, the variables of the diet composition table are in green, variables of the activity-budget table are in red and variables of the pattern of strata use table are in blue. The two first axis of the reference structure result from the simultaneous analysis of the three ecological tables and thus represents the habitat and resources use by the group. mDC = monthly diet composition; mAB = monthly activity-budget; mPSU = monthly pattern of strata use.</p
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