Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans

"Wordplay" in Ancient Near Eastern texts

Abstract: This book has three intersecting goals. First, it aims to provide the tools necessary for a comparative, in-depth study of “wordplay” in ancient Near Eastern texts. Second, it aspires to establish comprehensive taxonomies for the many kinds of devices that scholars have labeled as “wordplay” and for their proposed functions. Finally, it seeks to establish a consistent terminology that will offer students and scholars of ancient Near Eastern languages a useful template for documenting and understanding the devices they discover, and scholars of other disciplines access to the sophisticated devices of ancient Near Eastern writers. This, I hope, will lead to greater precision and interdisciplinary dialogue. The astute reader will notice that I have placed the term “wordplay” in quotation marks. It is my contention that the term is problematic for many reasons, which I discuss in chapter 1. Nevertheless, I find it heuristically useful in communicating to those outside the discipline what sorts of devices this book will examine, even if the devices differ in technique and their functions and social contexts appear alien. Readers also will note that I have opted to use the word texts, in the title rather than literature. There are two reasons for this. First, one finds “wordplay” in texts of all kinds, including annals, letters, law codes, medical prescriptions, omen lists, and ritual descriptions. In fact, there appear to be no generic or chronological restrictions to the application of “wordplay” in the ancient Near East. A second reason is that the social background of textual production, which I discuss in the chapter 2, strongly suggests that many forms of “wordplay” have an illocutionary function. Thus “wordplay” is often as much a performative phenomenon as a literary one. It is rather ironic that the presence of “wordplay” in ancient Near Eastern texts has been recognized for many years—in the case of the Hebrew Bible, for several centuries. Yet, large-scale publications on the phenomenon are rare. In addition, though we have benefitted from numerous articles on the subject, most have focused on select biblical passages rather than books. Moreover, until recently, most scholars were content merely to illustrate examples without discussing their functions, generic environments, or literary and social contexts. Consequently, despite the long-standing recognition, it is fair to say that many aspects of “wordplay” in ancient Near Eastern texts remain largely unexplored. Moreover, the disciplines represented in this study have long suffered from a vague, inconsistent, and, at times, even contradictory vocabulary that has done little to advance the study of the phenomena and all their permutations and effects. Consequently, many publications employ only the most basic terms for a number of devices that deserve individual attention. Thus, we find studies on alliteration that more accurately contain cases of homoeopropheron, homoioteleuton, parasonance, and the like, and publications on punning that ignore the visual register and do not distinguish devices of sound from those of meaning. It is my hope that this monograph will provide tools for advancing the comparative study of these phenomena with greater accuracy

Lurking Lions and Hidden Herds: Concealed Wisdom in the Hebrew Bible

This article presents evidence for a previously unrecognized literary device in the Book of Proverbs, in which texts that cluster references to animals also contain additional paronomastic allusions to animals. This device accords with the proverbs’ instruction to search for hidden knowledge, and resonates with their emphasis on the study of wild animals as a source of divine wisdom. The device also appears in psalms and prophecies, where it generally entails references to domesticated animals; here, the function appears to be rhetorical or performative. These groupings of concealed allusions to animals also add to the growing number of examples of the textual device of clustering