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Abstract Background Inherited vitreoretinopathies arise as a consequence of congenital retinal vascularisation abnormalities. They represent a phenotypically and genetically heterogeneous group of disorders that can have a major impact on vision. Several genes encoding proteins and effectors of the canonical Wnt/β-catenin pathway have been associated and precise diagnosis, although difficult, is essential for proper clinical management including syndrome specific management where appropriate. This work aimed to investigate the molecular basis of disease in a single proband born to consanguineous parents, who presented with microphthalmia, persistent foetal vasculature, posterior lens vacuoles, vitreoretinal dysplasia, microcephaly, hypotelorism and global developmental delay, and was registered severely visually impaired by 5 months of age. Methods Extensive genomic pre-screening, including microarray comparative genomic hybridisation and sequencing of a 114 gene panel associated with cataract and congenital ophthalmic disorders was conducted by an accredited clinical laboratory. Whole exome sequencing (WES) was undertaken on a research basis and in vitro TOPflash transcriptional reporter assay was utilised to assess the impact of the putative causal variant. Results In the proband, WES revealed a novel, likely pathogenic homozygous mutation in the cadherin-associated protein beta-1 gene (CTNNB1), c.884C>G; p.(Ala295Gly), which encodes a co-effector molecule of the Wnt/β-catenin pathway. The proband’s parents were shown to be heterozygous carriers but ophthalmic examination did not detect any abnormalities. Functional assessment of the missense variant demonstrated significant reduction of β-catenin activity. Conclusions This is the first report of a biallelic disease-causing variation in CTNNB1. We conclude that this biallelic, transcriptional inactivating mutation of CTNNB1 causes a severe, syndromic form of microphthalmia, persistent foetal vasculature and vitreoretinal dysplasia that results in serious visual loss in infancy.

Purpose: The objective of this paper is to provide a systematic literature review of recent developments in methodological frameworks for the modelling and simulation of agent-based advanced supply chain planning systems.Design/methodology/approach: A systematic literature review is provided to identify, select and make an analysis and a critical summary of all suitable studies in the area. It is organized into two blocks: the first one covers agent-based supply chain planning systems in general terms, while the second one specializes the previous search to identify those works explicitly containing methodological aspects.Findings: Among sixty suitable manuscripts identified in the primary literature search, only seven explicitly considered the methodological aspects. In addition, we noted that, in general, the notion of advanced supply chain planning is not considered unambiguously, that the social and individual aspects of the agent society are not taken into account in a clear manner in several studies and that a significant part of the works are of a theoretical nature, with few real-scale industrial applications. An integrated framework covering all phases of the modelling and simulation process is still lacking in the literature visited.Research limitations/implications: The main research limitations are related to the period covered (last four years), the selected scientific databases, the selected language (i.e. English) and the use of only one assessment framework for the descriptive evaluation part.Practical implications: The identification of recent works in the domain and discussion concerning their limitations can help pave the way for new and innovative researches towards a complete methodological framework for agent-based advanced supply chain planning systems.Originality/value: As there are no recent state-of-the-art reviews in the domain of methodological frameworks for agent-based supply chain planning, this paper contributes to systematizing and consolidating what has been done in recent years and uncovers interesting research gaps for future studies in this emerging field.