Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination

Pathogenic germline mutations in the RAD51 paralog genes RAD51C and RAD51D, are known to confer susceptibility to ovarian and triple-negative breast cancer. Here, we investigated whether germline loss-of-function variants affecting another RAD51 paralog gene, RAD51B, are also associated with breast and ovarian cancer. Among 3422 consecutively accrued breast and ovarian cancer patients consented to tumor/germline sequencing, the observed carrier frequency of loss-of-function germline RAD51B variants was significantly higher than control cases from the gnomAD population database (0.26% vs 0.09%), with an odds ratio of 2.69 (95% CI: 1.4–5.3). Furthermore, we demonstrate that tumors harboring biallelic RAD51B alteration are deficient in homologous recombination DNA repair deficiency (HRD), as evidenced by analysis of sequencing data and in vitro functional assays. Our findings suggest that RAD51B should be considered as an addition to clinical germline testing panels for breast and ovarian cancer susceptibility

Recessive ACTA1 variant causes congenital muscular dystrophy with rigid spine.

Variants in ACTA1, which encodes α-skeletal actin, cause several congenital myopathies, most commonly nemaline myopathy. Autosomal recessive variants comprise approximately 10% of ACTA1 myopathy. All recessive variants reported to date have resulted in loss of skeletal α-actin expression from muscle and severe weakness from birth. Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1. Skeletal α-actin expression was preserved in these patients. This report expands the clinical and histological phenotype of ACTA1 disease to include congenital muscular dystrophy with rigid spine and dystrophic features on muscle biopsy. This represents a new class of recessive ACTA1 variants, which do not abolish protein expression

“Only God Knows” : the emergence of a family movement against state violence in Libya

This study investigates how individuals organize against state violence in the context of an authoritarian state through an examination of the development of the “Association of the Families of the Martyrs of the Abū Salīm Prison Massacre” in Libya. This association of families was formed in 2007 to seek knowledge of the whereabouts of forcibly disappeared and imprisoned relatives who are believed to be victims in a contested massacre at Abū Salīm Prison in 1996. For years, families visited the prison, bringing packages of food and clothing, in the hopes of visiting their disappeared relatives. Their persistence, from inquiring about their relatives’ whereabouts to eventually organizing public demonstrations, constituted an unprecedented public resistance to the regime of Mu‘amar Gaddafi, who ruled one of the world’s most repressive authoritarian systems for over forty years. Through interviews with members of the family association from both eastern and western regions of the country, I trace how the organization emerged through connections between families in Libya. This case illustrates how an important form of collective mobilization rests in the context of the family, for which I develop the term “family movements.” I argue that family movements, which can include mobilizations exclusively among mothers or can more broadly encompass mobilizations that draw on any relation of kinship, represent a significant mode of collective action in authoritarian states cross-nationally. This analysis has implications for many sites, as for example in Latin America, where disappearance has been an integral strategy of state repression. Despite the power of forced disappearance as a mode of effacing political dissidence, the practice produces several unintended consequences. Namely, the absent body prevents families from experiencing closure, the ambiguity of which opens a space for the relatives left behind to mobilize. The uncertainty of death, and the protracted mourning process it induces, as well as the ongoing inquiries of the families sustain mobilization in a way that social movement scholars have not fully recognized. This study therefore contributes to our understandings of forced disappearance as a strategy of repression and explores the central role of the families in contesting this form of state violence.Sociolog