Transmission of an FMR1 premutation allele in a large family identified through newborn screening

The role of AGG interruptions

Carolyn M. Yrigollen, Guadalupe Mendoza-Morales, Randi J Hagerman, Flora Tassone

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The CGG repeat within the premutation range in the fragile X mental retardation 1 (FMR1) gene can lead to neurodegenerative disorders and intellectual disabilities. An increase in size upon the transmission from parent to child is more likely to occur for larger alleles and without AGG interruptions. We describe the molecular structure and the transmission of an FMR1 premutation allele in a multigenerational family, identified through newborn screening for fragile X syndrome. Transmission of the premutation allele was traced through five generations in 14 of the 23 individuals who were genotyped through cascade testing. Allele size instability during transmission was observed, but no expansions to a full mutation were detected. Clinical and molecular characterizations of the participants lead to the diagnosis of fragile X-Associated tremor ataxia syndrome in one subject identified as a premutation carrier. A gradual small increase in the size of the premutation allele was observed during transmission through five generations. The relative stability is likely due to the presence of two AGGs within the allele. The detection of AGG interruptions within the premutation alleles is important in genetic counseling, to better predict the risk of expansion during transmission from a premutation to a full-mutation allele.

Original languageEnglish (US)
Pages (from-to)553-559
Number of pages7
JournalJournal of Human Genetics
Volume58
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

Intellectual Disability
Alleles
Newborn Infant
Fragile X Syndrome
Mutation
Genetic Counseling
Molecular Structure
Neurodegenerative Diseases
Genes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Transmission of an FMR1 premutation allele in a large family identified through newborn screening : The role of AGG interruptions. / Yrigollen, Carolyn M.; Mendoza-Morales, Guadalupe; Hagerman, Randi J; Tassone, Flora.

In: Journal of Human Genetics, Vol. 58, No. 8, 08.2013, p. 553-559.

Research output: Contribution to journalArticle

@article{7e14ed7fa5034043a53297a8e8066137,
title = "Transmission of an FMR1 premutation allele in a large family identified through newborn screening: The role of AGG interruptions",
abstract = "The CGG repeat within the premutation range in the fragile X mental retardation 1 (FMR1) gene can lead to neurodegenerative disorders and intellectual disabilities. An increase in size upon the transmission from parent to child is more likely to occur for larger alleles and without AGG interruptions. We describe the molecular structure and the transmission of an FMR1 premutation allele in a multigenerational family, identified through newborn screening for fragile X syndrome. Transmission of the premutation allele was traced through five generations in 14 of the 23 individuals who were genotyped through cascade testing. Allele size instability during transmission was observed, but no expansions to a full mutation were detected. Clinical and molecular characterizations of the participants lead to the diagnosis of fragile X-Associated tremor ataxia syndrome in one subject identified as a premutation carrier. A gradual small increase in the size of the premutation allele was observed during transmission through five generations. The relative stability is likely due to the presence of two AGGs within the allele. The detection of AGG interruptions within the premutation alleles is important in genetic counseling, to better predict the risk of expansion during transmission from a premutation to a full-mutation allele.",
author = "Yrigollen, {Carolyn M.} and Guadalupe Mendoza-Morales and Hagerman, {Randi J} and Flora Tassone",
year = "2013",
month = "8",
doi = "10.1038/jhg.2013.50",
language = "English (US)",
volume = "58",
pages = "553--559",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Transmission of an FMR1 premutation allele in a large family identified through newborn screening

T2 - The role of AGG interruptions

AU - Yrigollen, Carolyn M.

AU - Mendoza-Morales, Guadalupe

AU - Hagerman, Randi J

AU - Tassone, Flora

PY - 2013/8

Y1 - 2013/8

N2 - The CGG repeat within the premutation range in the fragile X mental retardation 1 (FMR1) gene can lead to neurodegenerative disorders and intellectual disabilities. An increase in size upon the transmission from parent to child is more likely to occur for larger alleles and without AGG interruptions. We describe the molecular structure and the transmission of an FMR1 premutation allele in a multigenerational family, identified through newborn screening for fragile X syndrome. Transmission of the premutation allele was traced through five generations in 14 of the 23 individuals who were genotyped through cascade testing. Allele size instability during transmission was observed, but no expansions to a full mutation were detected. Clinical and molecular characterizations of the participants lead to the diagnosis of fragile X-Associated tremor ataxia syndrome in one subject identified as a premutation carrier. A gradual small increase in the size of the premutation allele was observed during transmission through five generations. The relative stability is likely due to the presence of two AGGs within the allele. The detection of AGG interruptions within the premutation alleles is important in genetic counseling, to better predict the risk of expansion during transmission from a premutation to a full-mutation allele.

AB - The CGG repeat within the premutation range in the fragile X mental retardation 1 (FMR1) gene can lead to neurodegenerative disorders and intellectual disabilities. An increase in size upon the transmission from parent to child is more likely to occur for larger alleles and without AGG interruptions. We describe the molecular structure and the transmission of an FMR1 premutation allele in a multigenerational family, identified through newborn screening for fragile X syndrome. Transmission of the premutation allele was traced through five generations in 14 of the 23 individuals who were genotyped through cascade testing. Allele size instability during transmission was observed, but no expansions to a full mutation were detected. Clinical and molecular characterizations of the participants lead to the diagnosis of fragile X-Associated tremor ataxia syndrome in one subject identified as a premutation carrier. A gradual small increase in the size of the premutation allele was observed during transmission through five generations. The relative stability is likely due to the presence of two AGGs within the allele. The detection of AGG interruptions within the premutation alleles is important in genetic counseling, to better predict the risk of expansion during transmission from a premutation to a full-mutation allele.

UR - http://www.scopus.com/inward/record.url?scp=84883271381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883271381&partnerID=8YFLogxK

U2 - 10.1038/jhg.2013.50

DO - 10.1038/jhg.2013.50

M3 - Article

VL - 58

SP - 553

EP - 559

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 8

ER -