Abstract
Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 190-197 |
| Number of pages | 8 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 167 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- Autoimmune disease
- CGG repeat
- FMR1 gene
- FXTAS
- Genetic counseling
- Premutation
- RNA toxicity
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Immune mediated disorders in women with a fragile X expansion and FXTAS. / Jalnapurkar, Isha; Rafika, Nuva; Tassone, Flora; Hagerman, Randi J.
In: American Journal of Medical Genetics, Part A, Vol. 167, No. 1, 01.01.2015, p. 190-197.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immune mediated disorders in women with a fragile X expansion and FXTAS
AU - Jalnapurkar, Isha
AU - Rafika, Nuva
AU - Tassone, Flora
AU - Hagerman, Randi J
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations.
AB - Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations.
KW - Autoimmune disease
KW - CGG repeat
KW - FMR1 gene
KW - FXTAS
KW - Genetic counseling
KW - Premutation
KW - RNA toxicity
UR - http://www.scopus.com/inward/record.url?scp=84919868162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919868162&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.36748
DO - 10.1002/ajmg.a.36748
M3 - Article
C2 - 25399540
AN - SCOPUS:84919868162
VL - 167
SP - 190
EP - 197
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
SN - 1552-4825
IS - 1
ER -