Carson Smith

“It didn’t feel like anything unusual because we had already been through so much”: Disability-related research experiences of families with children enrolled in the undiagnosed diseases network

Kevin Mintz, Elisa N. Altamirano, Meghan C. Halley, Krysta S. Barton et autres

PURPOSE: In recent years, researchers have brought attention to the underrepresentation of people with disabilities in biomedical research, including genomics research. However, little is known about how disability-related experiences influence participation in rare disease research. This omission is striking because rare diseases …

us (code pays fourni par la source)

Uncovering phenotypic expansion in AXIN2-related disorders through precision animal modeling

Nathalie M. Aceves, Denise G. Lanza, Paul C. Marcogliese, Di Lu et autres

PURPOSE: Heterozygous pathogenic variants in AXIN2 (HGNC: 904) cause oligodontia-colorectal cancer syndrome. We identified 5 individuals with de novo heterozygous variants [NM_004655.4:c.196G>A p.(Glu66Lys), c.197A>G p.(Glu66Gly), and c.199G>A p.(Gly67Arg)] in AXIN2. Common phenotypes among these individuals included ectodermal dysplasia, global developmental delay, microcephaly, …

us, ca, gb (code pays fourni par la source)

Compound genetic burden in oculo-facio-cardio-dental (OFCD) syndrome: surgical risk stratification with co-occurring BCOR and MYLK mutations

Sujin Kang, Alejandro M Perez, Carson Smith, Ta Chen Chang et autres

Introduction Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant disorder caused by pathogenic BCOR variants and characterized by congenital cataracts, microcornea, and secondary glaucoma. Multilocus pathogenic variation (MPV), in which independent variants contribute to disease burden, can further complicate syndromic presentations and …

us (code pays fourni par la source)

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

Isabelle Cooperstein, Shruti Marwaha, Alistair Ward, Shilpa N. Kobren et autres

BACKGROUND: Exome sequencing (ES) and genome sequencing (GS) are increasingly used as standard genetic tests to identify diagnostic variants in rare disease cases. However, prioritizing these variants to reduce the time and burden of manual interpretation by clinical teams remains a significant …

us, gb (code pays fourni par la source)

Joint, multifaceted genomic analysis enables diagnosis of diverse, ultra-rare monogenic presentations

Shilpa N. Kobren, Mikhail A. Moldovan, Rebecca Reimers, Daniel Traviglia et autres

Genomics for rare disease diagnosis has advanced at a rapid pace due to our ability to perform in-depth analyses on individual patients with ultra-rare diseases. The increasing sizes of ultra-rare disease cohorts internationally newly enables cohort-wide analyses for new discoveries, but well-calibrated …

us, nl, es (code pays fourni par la source)

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients

Lane Fitzsimmons, Maria T. Acosta, David R. Adams, Ben Afzali et autres

BACKGROUND: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the …

us (code pays fourni par la source)

P265: Exploring ophthalmological diagnoses in the Undiagnosed Diseases Network: Insights and implications

Stephanie Bivona, Carson Smith, Nicholas A. Borja, Güney Bademci et autres

Inherited ocular diseases are characterized by numerous conditions, including inherited retinal disorders (IRDs) and congenital ocular malformations. These conditions can present as non-syndromic or syndromic, and identifying the genetic causes of these conditions is complicated by allelic and locus heterogeneity. Access to …

us (code pays fourni par la source)

Advancing Equity in Rare Disease Research: Insights From the Undiagnosed Disease Network

Nicholas A. Borja, Rory J. Tinker, Stephanie Bivona, Carson Smith et autres

Rare diseases affect 6%-8% of the population and present diagnostic challenges, particularly for historically marginalized ethnic and racial groups. The Undiagnosed Diseases Network (UDN) aims to enhance diagnosis rates and research participation among such minoritized groups. A retrospective review was conducted from …

us (code pays fourni par la source)

Gene therapy for hereditary deafness

Carson Smith, Mohammad Faraz Zafeer, Mustafa Tekin

us (code pays fourni par la source)

Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities

Matthew J. Moulton, Kristhen N Atala, Yiming Zheng, Debdeep Dutta et autres

us (code pays fourni par la source)

P254: Exome sequencing as a first-tier approach for rare forms of syndromic hearing loss

Carson Smith, Dayna Morel Swols, LéShon Peart, Memoona Ramzan et autres

Hearing loss (HL) is a common sensory impairment that affects approximately 50% of the population in their lifetime. With more than half of congenital or early childhood-onset sensorineural HL attributed to genetic factors, advances in genetic testing have allowed etiologic diagnosis, leading …

us (code pays fourni par la source)

O23: Diagnostic success of genomic analyses in adults with undiagnosed diseases: A report from the Undiagnosed Diseases Network (UDN)

Stephanie Bivona, Carson Smith, Güney Bademci, LéShon Peart et autres

Undiagnosed diseases present unique clinical management challenges due to their rarity and complexity. Approximately eighty percent of undiagnosed diseases are thought to have a genetic etiology. Historically, methods to assist in diagnosing individuals have included whole exome and whole genome sequencing (WES/WGS). …

us (code pays fourni par la source)