Delineating the expanding phenotype of HERC2-related disorders: The impact of biallelic loss of function versus missense variation.

HECT And RLD Domain-Containing E3 Ubiquitin Protein Ligase 2, or HERC2, codes an ubiquitin ligase that has an important role in key cellular processes including cell cycle regulation, DNA repair, mitochondrial functions, and spindle formation during mitosis. While HERC2 Neurodevelopmental Disorder in Old Order Amish is a well characterized human disorder involving HERC2, bi-allelic HERC2 loss of function has only been described in three families and results in a more severe neurodevelopmental disorder. Herein, we delineate the HERC2 loss of function phenotype by describing three previously unreported patients, and by summarizing the molecular and phenotypic information of all known HERC2 missense variants and biallelic loss of function patients. Collectively, these twelve individuals present with recurring features that define a syndrome with varying combinations of severe neurodevelopmental delay, structural brain anomalies, seizures, hypotonia, feeding difficulties, hearing and vision issues, and renal anomalies. This study describes a distinct neurodevelopmental disorder, emphasizing the importance of further characterization of HERC2-related disorders, as well as highlighting the importance of ongoing work into understanding these critical neurodevelopmental pathways.

Urologists' Current Practices in Screening and Treating Men With a Family History of Prostate Cancer.

OBJECTIVE: To assess urologists' knowledge and utilization of family history to determine prostate cancer (PC) screening and treatment recommendations. MATERIALS AND METHODS: Questionnaires that explored urologists' knowledge, frequency, and utilization of family history information for screening and treatment recommendations for PC were prospectively collected. Data were summarized and compared using descriptive statistics. RESULTS: A total of 87 responses were collected, for a response rate of 60% (87 of 145). The majority of urologists reported that they always collect family history when discussing risk (95%) or screening (87%), and recommended earlier screening for men with family history of PC in comparison with men with no family history. Although only 57% reported always collecting family history when discussing treatment, the majority of respondents reported that a positive family history influenced their treatment recommendations. Eight percent of urologists would recommend prostatectomy for men diagnosed with low-grade, low-risk PC and no family history of PC vs 52% who would recommend the same course of treatment when the patient had at least 1 first-degree relative who died of the disease. Conversely, 91% of urologists would recommend active surveillance for men with low-grade, low-risk PC and no family history vs 47% for those with at least 1 first-degree relative who died of the disease. CONCLUSION: The majority of urologists collect information on family history of PC. Despite the lack of literature to support that patients with familial PC require more aggressive treatment, urologists were more likely to recommend definitive therapies.