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The X-linked PTCHD1 gene, encoding a synaptic membrane protein, has been involved in neurodevelopmental disorders with the description of deleterious genomic microdeletions or truncating coding mutations. Missense variants were also identified, however, without any functional evidence supporting their pathogenicity level. We investigated 13 missense variants of PTCHD1, including eight previously described (c.152G>A,p.(Ser51Asn); c.217C>T,p.(Leu73Phe); c.517A>G,p.(Ile173Val); c.542A>C,p.(Lys181Thr); c.583G>A,p.(Val195Ile); c.1076A>G,p.(His359Arg); c.1409C>A,p.(Ala470Asp); c.1436A>G,p.(Glu479Gly)), and five novel ones (c.95C>T,p.(Pro32Leu); c.95C>G,p.(Pro32Arg); c.638A>G,p.(Tyr213Cys); c.898G>C,p.(Gly300Arg); c.928G>C,p.(Ala310Pro)) identified in male patients with intellectual disability (ID) and/or autism spectrum disorder (ASD). Interestingly, several of these variants involve amino acids localized in structural domains such as transmembrane segments. To evaluate their potentially deleterious impact on PTCHD1 protein function, we performed in vitro overexpression experiments of the wild-type and mutated forms of PTCHD1-GFP in HEK 293T and in Neuro-2a cell lines as well as in mouse hippocampal primary neuronal cultures. We found that six variants impaired the expression level of the PTCHD1 protein, and were retained in the endoplasmic reticulum suggesting abnormal protein folding. Our functional analyses thus provided evidence of the pathogenic impact of missense variants in PTCHD1, which reinforces the involvement of the PTCHD1 gene in ID and in ASD., (© 2021 The Authors. Human Mutation published by Wiley Periodicals LLC.)

Destined for healthcare professionals interested in public health policy in developing countries, E-med is one of the few francophone forums on essential medicines. Bringing together users with diverse backgrounds, discussion groups illustrate the effects of globalization on health policy: disappearance of distance, convergence of political and sanitary issues, enhanced cooperation between public and private sectors, coalitions of heterogeneous players and destruction of national and international barriers. Having benefited from the development of the Internet in recent years, as a secondary tool, E-med, must now evolve with this tool that is now ubiquitous in international health policy.

Since the end of the cold war the tone of international relations has clearly changed. Whereas relations were once defined strictly in terms of more or less armed confrontation, economic and social issues now play a growing role. Healthcare policies in Africa have long been influenced by the policies of countries sponsoring bilateral and even multilateral foreign aid programs. However the last ten years have witnessed an increasing interaction between international policy and healthcare policy. The two main reasons for this trend involve 1) access to drug treatment and the WTO and 2) the extension and impact of the AIDS epidemic. The problem of access to drug treatment for poor populations (fundamental right) has led to the emergence of an increasingly strong and effective civil society. Because of its social and economic effects as well as its geopolitical and security implications, AIDS has become a major factor in international relations. With regard to both these issues the place and role of the USA is demonstrative of the interaction between healthcare and international relations.