Genotype/phenotype relationships in FXTAS

Emily G. Allen, Maureen A. Leehey, Flora Tassone, Stephanie Sherman

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

In this chapter we explore the effects of molecular measures of the FMR1 gene on clinical, cognitive, radiological, and pathological phenotypes associated with fragile X-associated tremor/ataxia syndrome (FXTAS). In addition to reviewing the FXTAS phenotype, we will also present methods that have been developed for quantifying severity of FXTAS symptoms, including development and use of the FXTAS rating scale, the neuropathy screening scale, and use of the CATSYS system to assess early, prodromal symptoms. In our review of phenotypic features, we focus primarily on studies in which findings were correlated with FMR1 molecular measures. The phenotypes considered include (1) clinical neurological measures, (2) cognitive measures with a focus on executive function, (3) psychiatric phenotypes, (4) radiological outcomes, and (5) pathological measures. Because women are more mildly affected than men and may, in fact, have a different presentation, we will review FXTAS among men and women separately. Overall, our goal in this chapter is to begin to define alleles that are “at risk” for FXTAS. Based on this review, it is clear that there is a strong correlation of the increasing risk for FXTAS with increasing repeat size. However, much work needs to be done to further define the properties of the CGG repeat sequence that contribute to increased risk and severity of symptoms of FXTAS among men and women.

Original languageEnglish (US)
Title of host publicationFXTAS, FXPOI, and Other Premutation Disorders
PublisherSpringer International Publishing
Pages129-160
Number of pages32
ISBN (Electronic)9783319338989
ISBN (Print)9783319338965
DOIs
StatePublished - Jan 1 2016

Fingerprint

Genotype
Phenotype
Screening
Genes
Prodromal Symptoms
Fragile X Tremor Ataxia Syndrome
Executive Function
Psychiatry
Alleles

Keywords

  • FMR1
  • FXTAS
  • Genotype/phenotype
  • Premutation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)

Cite this

Allen, E. G., Leehey, M. A., Tassone, F., & Sherman, S. (2016). Genotype/phenotype relationships in FXTAS. In FXTAS, FXPOI, and Other Premutation Disorders (pp. 129-160). Springer International Publishing. https://doi.org/10.1007/978-3-319-33898-9_7

Genotype/phenotype relationships in FXTAS. / Allen, Emily G.; Leehey, Maureen A.; Tassone, Flora; Sherman, Stephanie.

FXTAS, FXPOI, and Other Premutation Disorders. Springer International Publishing, 2016. p. 129-160.

Research output: Chapter in Book/Report/Conference proceedingChapter

Allen, EG, Leehey, MA, Tassone, F & Sherman, S 2016, Genotype/phenotype relationships in FXTAS. in FXTAS, FXPOI, and Other Premutation Disorders. Springer International Publishing, pp. 129-160. https://doi.org/10.1007/978-3-319-33898-9_7
Allen EG, Leehey MA, Tassone F, Sherman S. Genotype/phenotype relationships in FXTAS. In FXTAS, FXPOI, and Other Premutation Disorders. Springer International Publishing. 2016. p. 129-160 https://doi.org/10.1007/978-3-319-33898-9_7
Allen, Emily G. ; Leehey, Maureen A. ; Tassone, Flora ; Sherman, Stephanie. / Genotype/phenotype relationships in FXTAS. FXTAS, FXPOI, and Other Premutation Disorders. Springer International Publishing, 2016. pp. 129-160
@inbook{785af2c312ac4b26b6d6f57145cea496,
title = "Genotype/phenotype relationships in FXTAS",
abstract = "In this chapter we explore the effects of molecular measures of the FMR1 gene on clinical, cognitive, radiological, and pathological phenotypes associated with fragile X-associated tremor/ataxia syndrome (FXTAS). In addition to reviewing the FXTAS phenotype, we will also present methods that have been developed for quantifying severity of FXTAS symptoms, including development and use of the FXTAS rating scale, the neuropathy screening scale, and use of the CATSYS system to assess early, prodromal symptoms. In our review of phenotypic features, we focus primarily on studies in which findings were correlated with FMR1 molecular measures. The phenotypes considered include (1) clinical neurological measures, (2) cognitive measures with a focus on executive function, (3) psychiatric phenotypes, (4) radiological outcomes, and (5) pathological measures. Because women are more mildly affected than men and may, in fact, have a different presentation, we will review FXTAS among men and women separately. Overall, our goal in this chapter is to begin to define alleles that are “at risk” for FXTAS. Based on this review, it is clear that there is a strong correlation of the increasing risk for FXTAS with increasing repeat size. However, much work needs to be done to further define the properties of the CGG repeat sequence that contribute to increased risk and severity of symptoms of FXTAS among men and women.",
keywords = "FMR1, FXTAS, Genotype/phenotype, Premutation",
author = "Allen, {Emily G.} and Leehey, {Maureen A.} and Flora Tassone and Stephanie Sherman",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/978-3-319-33898-9_7",
language = "English (US)",
isbn = "9783319338965",
pages = "129--160",
booktitle = "FXTAS, FXPOI, and Other Premutation Disorders",
publisher = "Springer International Publishing",

}

TY - CHAP

T1 - Genotype/phenotype relationships in FXTAS

AU - Allen, Emily G.

AU - Leehey, Maureen A.

AU - Tassone, Flora

AU - Sherman, Stephanie

PY - 2016/1/1

Y1 - 2016/1/1

N2 - In this chapter we explore the effects of molecular measures of the FMR1 gene on clinical, cognitive, radiological, and pathological phenotypes associated with fragile X-associated tremor/ataxia syndrome (FXTAS). In addition to reviewing the FXTAS phenotype, we will also present methods that have been developed for quantifying severity of FXTAS symptoms, including development and use of the FXTAS rating scale, the neuropathy screening scale, and use of the CATSYS system to assess early, prodromal symptoms. In our review of phenotypic features, we focus primarily on studies in which findings were correlated with FMR1 molecular measures. The phenotypes considered include (1) clinical neurological measures, (2) cognitive measures with a focus on executive function, (3) psychiatric phenotypes, (4) radiological outcomes, and (5) pathological measures. Because women are more mildly affected than men and may, in fact, have a different presentation, we will review FXTAS among men and women separately. Overall, our goal in this chapter is to begin to define alleles that are “at risk” for FXTAS. Based on this review, it is clear that there is a strong correlation of the increasing risk for FXTAS with increasing repeat size. However, much work needs to be done to further define the properties of the CGG repeat sequence that contribute to increased risk and severity of symptoms of FXTAS among men and women.

AB - In this chapter we explore the effects of molecular measures of the FMR1 gene on clinical, cognitive, radiological, and pathological phenotypes associated with fragile X-associated tremor/ataxia syndrome (FXTAS). In addition to reviewing the FXTAS phenotype, we will also present methods that have been developed for quantifying severity of FXTAS symptoms, including development and use of the FXTAS rating scale, the neuropathy screening scale, and use of the CATSYS system to assess early, prodromal symptoms. In our review of phenotypic features, we focus primarily on studies in which findings were correlated with FMR1 molecular measures. The phenotypes considered include (1) clinical neurological measures, (2) cognitive measures with a focus on executive function, (3) psychiatric phenotypes, (4) radiological outcomes, and (5) pathological measures. Because women are more mildly affected than men and may, in fact, have a different presentation, we will review FXTAS among men and women separately. Overall, our goal in this chapter is to begin to define alleles that are “at risk” for FXTAS. Based on this review, it is clear that there is a strong correlation of the increasing risk for FXTAS with increasing repeat size. However, much work needs to be done to further define the properties of the CGG repeat sequence that contribute to increased risk and severity of symptoms of FXTAS among men and women.

KW - FMR1

KW - FXTAS

KW - Genotype/phenotype

KW - Premutation

UR - http://www.scopus.com/inward/record.url?scp=85018935292&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018935292&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-33898-9_7

DO - 10.1007/978-3-319-33898-9_7

M3 - Chapter

AN - SCOPUS:85018935292

SN - 9783319338965

SP - 129

EP - 160

BT - FXTAS, FXPOI, and Other Premutation Disorders

PB - Springer International Publishing

ER -