Exile Vol. XI No. 1

FICTION By the Fire of the Chief by Peggy Schmidt 9-17 From the Diary of a Vanishing Man by Ed Brunner 19-29 Dialogue by Ken Booth 35-37 POETRY Johnny Joe by Bill West 6-7 Caterpillar by Barb Bergantz 17 Poem by Bonnie McCarthy 29 The Queen by Hugh Wilder 31 The Clown by Barb Bergantz 32 Poem by Gretchen Schenck 33 Treatise on Cosmology by P. M. Grout 37 Stimulus by Susan Sherwood 37 Depot by Susan Sherwood 39 GRAPHICS Pen and Ink by Dave Goodwin 7 Pen and Ink by Ramona Gibbs 8 Pen and Ink by Tod Riddell 18 Charcoal by Dave Goodwin 30 Woodcut by Parker Waite III 34 Woodcut by Lela Giles 3

Exile Vol. XII No. 1

POETRY Elsinore by Alan Pavlik 8 Geraniums in Winter by Tom Getz 9 Clytemnestra by Sharon Hornberger 11-12 Panes by Bonnie Bishop 12 Vantage Point by Hugh Wilder 17 The Return by Alan Pavlik 18 Chiaroscuro by Bonnie Bishop 23 Poem by Gretchen Schenck 24 Waiting to Die by Kit Andrews 25 Poem by Trudi Spaeth 32 Dragon by Barbara Bergantz 33 After Alice by Barbara Bergantz 41-42 Reeds by Lauren Shakely 42 Inferno by Hugh Wilder 44 FICTION That Horrible War-Dream by James Jacobi 5-7 In a Family Way by Kathy Swiger 13-16 George by Buck Niehoff 19-23 Perfection by Susan Kurtz 27-32 Blue in Green by Alan Pavlik 35-40 The Streetcar Named Desire by Cem Kozlu 45-46 ART Whoever Dies, Dies in Pain by Nedra Veatch 4 Job and Patientia by Dan Thaxton 10 Specimen by David Goodwin 17 Isabel by Mary Davidson 26 Birds by Clare Conrad 34 Eli, Eli, Lama Sabacthani by Dan Thaxton Cover design by Jamie Foste

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome