Abstract
The RNA-based disorders of muscle and brain include myotonic dystrophy type 1 and type 2 (dystrophia myotonica, DM) and fragile X-associated tremor/ataxia syndrome (FXTAS). These disorders reflect an emerging concept in the pathogenesis of genetic disease, namely, that an expanded repeat element within a noncoding portion of an RNA transcript can be directly responsible for a disease phenotype. DM is an autosomal-dominant disorder and the most common form of muscular dystrophy in adults. The DM protein kinase gene (DMPK) and the zinc-finger protein 9 gene (ZNF9) are responsible for DM type1 and DM type 2 respectively. The discovery of the second gene (ZNF9) on a separate chromosome from the DMPK gene, which gives rise to many of the same clinical features, considerably strengthened the argument for an RNA-based mechanism for DM pathogenesis. FXTAS is caused by an RNA-based pathogenesis due to an expanded (noncoding) trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene. Abnormal expression of the fragile X mental retardation 1 (FMR1) gene leads to both the neurodegenerative FXTAS and fragile X syndrome. FXTAS is a movement disorder that affects some carriers of premutation alleles of the FMR1 gene. The disorder generally presents with progressive intention tremor and/or gait ataxia and Parkinsonism.
| Original language | English (US) |
|---|---|
| Title of host publication | Neurobiology of Disease |
| Publisher | Elsevier Inc. |
| Pages | 125-133 |
| Number of pages | 9 |
| ISBN (Print) | 9780120885923 |
| DOIs | |
| State | Published - 2007 |
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ASJC Scopus subject areas
- Dentistry(all)
- Medicine(all)
Cite this
RNA-based disorders of muscle and brain. / Hagerman, Paul J.
Neurobiology of Disease. Elsevier Inc., 2007. p. 125-133.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - RNA-based disorders of muscle and brain
AU - Hagerman, Paul J
PY - 2007
Y1 - 2007
N2 - The RNA-based disorders of muscle and brain include myotonic dystrophy type 1 and type 2 (dystrophia myotonica, DM) and fragile X-associated tremor/ataxia syndrome (FXTAS). These disorders reflect an emerging concept in the pathogenesis of genetic disease, namely, that an expanded repeat element within a noncoding portion of an RNA transcript can be directly responsible for a disease phenotype. DM is an autosomal-dominant disorder and the most common form of muscular dystrophy in adults. The DM protein kinase gene (DMPK) and the zinc-finger protein 9 gene (ZNF9) are responsible for DM type1 and DM type 2 respectively. The discovery of the second gene (ZNF9) on a separate chromosome from the DMPK gene, which gives rise to many of the same clinical features, considerably strengthened the argument for an RNA-based mechanism for DM pathogenesis. FXTAS is caused by an RNA-based pathogenesis due to an expanded (noncoding) trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene. Abnormal expression of the fragile X mental retardation 1 (FMR1) gene leads to both the neurodegenerative FXTAS and fragile X syndrome. FXTAS is a movement disorder that affects some carriers of premutation alleles of the FMR1 gene. The disorder generally presents with progressive intention tremor and/or gait ataxia and Parkinsonism.
AB - The RNA-based disorders of muscle and brain include myotonic dystrophy type 1 and type 2 (dystrophia myotonica, DM) and fragile X-associated tremor/ataxia syndrome (FXTAS). These disorders reflect an emerging concept in the pathogenesis of genetic disease, namely, that an expanded repeat element within a noncoding portion of an RNA transcript can be directly responsible for a disease phenotype. DM is an autosomal-dominant disorder and the most common form of muscular dystrophy in adults. The DM protein kinase gene (DMPK) and the zinc-finger protein 9 gene (ZNF9) are responsible for DM type1 and DM type 2 respectively. The discovery of the second gene (ZNF9) on a separate chromosome from the DMPK gene, which gives rise to many of the same clinical features, considerably strengthened the argument for an RNA-based mechanism for DM pathogenesis. FXTAS is caused by an RNA-based pathogenesis due to an expanded (noncoding) trinucleotide repeat in the fragile X mental retardation 1 (FMR1) gene. Abnormal expression of the fragile X mental retardation 1 (FMR1) gene leads to both the neurodegenerative FXTAS and fragile X syndrome. FXTAS is a movement disorder that affects some carriers of premutation alleles of the FMR1 gene. The disorder generally presents with progressive intention tremor and/or gait ataxia and Parkinsonism.
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U2 - 10.1016/B978-012088592-3/50013-X
DO - 10.1016/B978-012088592-3/50013-X
M3 - Chapter
SN - 9780120885923
SP - 125
EP - 133
BT - Neurobiology of Disease
PB - Elsevier Inc.
ER -