Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

A Function - Behaviour - Structure View of Social Situated Design Agents

This paper proposes a comprehensive schema to represent an agent's social knowledge using the Function - Behaviour Structure (FBS) schema. Although this schema has originally been developed to represent knowledge about design objects, it is sufficiently abstract to also describe knowledge about agents. This paper shows how such an FBS view can be useful to support the interaction of situated design agents

A Framework for Situated Design Agents

This paper presents the beginnings of a framework to enhance our understanding of situated design agents. It builds on the function-behaviour-structure (FBS) schema to represent essential concepts of situated designing. Our framework covers different stages in the life-cycle of situated design agents, including their development, testing and usage

Team expertise from individual expertise (through social interactions in computational agents)

This paper proposes a model of expertise of temporary design teams. It is based on a situated view of knowledge as being grounded in individual experience, which emphasises its applicability and teleology. The paper describes situated knowledge and expertise using the function-behaviour-structure (FBS) schema. It then outlines how the FBS schema can be used to model expertise of temporary teams as emerging from the interaction of individual experts

Situated Agent Communication for Design

This paper outlines an approach to communication among design agents in a multi-agent environment. This approach is founded on the concepts of situatedness from cognitive science and is an extension of traditional multi-agent communication

A Process Framework Of Affordances In Design

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Representational Affordances In Design, With Examples From Analogy Making And Optimization

Affordances in design can be understood as the action possibilities of a user interacting with a designed object. In this paper, we develop the notion of 'representational affordances' to denote affordances provided by design representations to the desi

Abstracting and formalising the design co-evolution model

Abstract Co-evolution accounts have generally been used to describe how problems and solutions both change during the design process. More generally, problems and solutions can be considered as analytic categories, where change is seen to occur within categories or across categories. There are more categories of interest than just problems and solutions, for example, the participants in a design process (such as members of a design team or different design teams) and categories defined by design ontologies (such as function-behaviour-structure or concept-knowledge). In this paper, we consider the co-evolution of different analytic categories (not just problems and solutions), by focussing on how changes to a category originate either from inside or outside that category. We then illustrate this approach by applying it to data from a single design session using three different systems of categorisation (problems and solutions, different designers and function, behaviour and structure). This allows us to represent the reciprocal influence of change within and between these different categories, while using a common notation and common approach to graphing quantitative data. Our approach demonstrates how research traditions that are currently distinct from each other (such as co-evolution, collaboration and function-behaviour-structure) can be connected by a single analytic approach.This work was supported by the US National Science Foundation (grant number CMMI- 1762415