Robert Weiss, Ph.D.
Our research focuses on the genetics and genomics of human neuromuscular disorders. Our laboratory studies patients with Duchenne muscular dystrophy (DMD), who suffer from progressive weakness and loss of both skeletal and heart muscle due to loss-of-function mutations in the dystrophin gene. Investigations of specific mutations has revealed novel mechanisms, including mutations that activate internal AUG start codons and intronic point mutations that couple pseudoexon inclusion with premature transcription termination. These studies are in anticipation of a new era of mutation-specific clinical trials and patient-specific therapeutics. Other interests include understanding how variation in the rest of the genome contributes to disease progression and severity in patients. We have participated several studies that describe SNPs in modifier genes that prolong ambulation in DMD boys.
We also studies families with autosomal dominant fascioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy resulting in progressive weakness in the face, shoulders, and hip girdle. FSHD has a unique pathogenic mechanism resulting from a contraction in the number of 3.3 kb D4Z4 macrosatellite repeats near the chromosome 4q telomere. Each D4Z4 repeat encodes a copy of the DUX4 gene, a transcriptional regulator that is toxic in muscle, and a repeat number of <10 results in epigenetic reactivation of the most distal DUX4 gene. One goal of our research is to better understand the variability in severity, onset, and progression of FSHD by identifying genes that modify these aspects of disease. To this end, we continue to study the historic Utah FSHD kindred first ascertained in the 1930s by Prof. Fayette Stephens, Utah’s “first” geneticist. The affected members of this large kindred all inherited a founder D4Z4 contraction from a single ancestor, who emigrated with his affected children to Salt Lake City between 1847 and 1856 with the Mormon pioneers.
Waldrop MA, Moore SA, Mathews KD, Darbro BW, Medne L, Finkel R, Connolly AM, Crawford TO, Drachman D, Wein N, Habib AA, Krzesniak-Swinarska MA, Zaidman CM, Collins JJ, Jokela M, Udd B, Day JW, Ortiz-Guerrero G, Statland J, Butterfield RJ, Dunn DM, Weiss RB, Flanigan KM. Intron mutations and early transcription termination in Duchenne and Becker muscular dystrophy. Hum Mutat. 2022 Feb 14;. doi: 10.1002/humu.24343. [Epub ahead of print] PubMed PMID: 35165973.
Johnson NE, Butterfield RJ, Mayne K, Newcomb T, Imburgia C, Dunn D, Duval B, Feldkamp ML, Weiss RB. Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program. Neurology. 2021 Feb 16;96(7):e1045-e1053. doi: 10.1212/WNL.0000000000011425. Epub 2021 Jan 20. PubMed PMID: 33472919; PubMed Central PMCID: PMC8055332.
Weiss RB, Vieland VJ, Dunn DM, Kaminoh Y, Flanigan KM. Long-range genomic regulators of THBS1 and LTBP4 modify disease severity in duchenne muscular dystrophy. Ann Neurol. 2018 Aug;84(2):234-245. doi: 10.1002/ana.25283. Epub 2018 Aug 25. PubMed PMID: 30014611; PubMed Central PMCID: PMC6168392.
Complete list at MyBibliography
Sr. Laboratory Specialist
Sr. Laboratory Specialist
Building/Office: EIHG 2260