Journal article
DMPK mRNA Expression in Human Brain Tissue Throughout the Lifespan
Neurology. Genetics, Vol.7(1), pp.e537-e537
02/2021
DOI: 10.1212/NXG.0000000000000537
PMCID: PMC7862092
PMID: 33575482
Abstract
Myotonic dystrophy is a multisystem disorder caused by a trinucleotide repeat expansion on the myotonic dystrophy protein kinase (
) gene. To determine whether wildtype DMPK expression patterns vary as a function of age, we analyzed DMPK expression in the brain from 99 donors ranging from 5 postconceptional weeks to 80 years old.
We used the BrainSpan messenger RNA sequencing and the Yale Microarray data sets, which included brain tissue samples from 42 and 57 donors, respectively. Collectively, donors ranged in age from 5 postconceptional weeks to 80 years old.
expression was normalized for each donor across regions available in both data sets. Restricted cubic spline linear regression models were used to analyze the effects of log-transformed age and sex on normalized
expression data.
Age was a statistically significant predictor of normalized
expression pattern in the human brain in the BrainSpan (
< 0.005) and Yale data sets (
< 0.005). Sex was not a significant predictor. Across both data sets, normalized wildtype
expression steadily increases during fetal development, peaks around birth, and then declines to reach a nadir around age 10.
Peak expression of
coincides with a time of dynamic brain development. Abnormal brain
expression due to myotonic dystrophy may have implications for early brain development.
Details
- Title: Subtitle
- DMPK mRNA Expression in Human Brain Tissue Throughout the Lifespan
- Creators
- Kathleen E Langbehn - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaZoe Carlson-Stadler - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaEllen van der Plas - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaMarco M Hefti - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaJeffrey D Dawson - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaDavid J Moser - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of IowaPeggy C Nopoulos - Department of Psychiatry (K.E.L., Z.C.-S., E.v.d.P., D.J.M., and P.C.N.), Department of Pathology (M.M.H.), Department of Pediatrics (P.C.N.), and Department of Neurology (P.C.N.), College of Public Health (J.D.D.), University of Iowa
- Resource Type
- Journal article
- Publication Details
- Neurology. Genetics, Vol.7(1), pp.e537-e537
- DOI
- 10.1212/NXG.0000000000000537
- PMID
- 33575482
- PMCID
- PMC7862092
- NLM abbreviation
- Neurol Genet
- ISSN
- 2376-7839
- eISSN
- 2376-7839
- Publisher
- United States
- Grant note
- K23 NS109284 / NINDS NIH HHS
- Language
- English
- Date published
- 02/2021
- Academic Unit
- Neurology; Public Health Administration; Psychiatry; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Biostatistics; Medicine Administration
- Record Identifier
- 9984071605002771
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