Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

From the earliest times, the political tradition of Islam, on the one hand as formulated in Islamic theology and law, on the other hand as expressed in the accepted versions of early Islamic history, contains two distinct and in some measure even contradictory principles concerning the problems of government and obedience, of which one might be described as authoritarian and quietist, the other as radical and activist. The exponents of both these principles point to the authority of the Qur'ān and tradition, and to the example of the Prophet himself. Both principles are indeed exemplified in the career and teachings of the Prophet and in the history of the early caliphate, which constitute the shared memorv and common heritage of Muslims everywhere. These two traditions may be examined separately.

La nature de la tolérance islamique — sa portée et ses limites — sont souvent mal comprises. Deux mythes courants, deux stéréotypes, s'opposent à ce propos : d'un côté, la vision d'un islam bigot, intolérant, tyrannique, symbolisé par l'image légendaire du guerrier fanatique déferlant du désert, le Coran dans une main et l'épée dans l'autre, et offrant à ses victimes le choix entre les deux ; de l'autre, celui de l'égalité des droits, de l'utopie interreligieuse et interraciale dans laquelle musulmans, chrétiens et juifs auraient collaboré dans un âge d'or de libre effort intellectuel.