Fragile X AGG analysis provides new risk predictions for 45-69 repeat alleles

被引：95

作者：

Nolin, Sarah L. ^{[1
]}

Sah, Sachin ^{[2
]}

Glicksman, Anne ^{[1
]}

Sherman, Stephanie L. ^{[3
]}

Allen, Emily ^{[3
]}

Berry-Kravis, Elizabeth ^{[4
]}

Tassone, Flora ^{[5
]}

Yrigollen, Carolyn ^{[5
]}

Cronister, Amy ^{[6
]}

Jodah, Marcia ^{[6
]}

Ersalesi, Nicole ^{[1
]}

Dobkin, Carl ^{[1
]}

Brown, W. Ted ^{[1
]}

Shroff, Raghav ^{[2
]}

Latham, Gary J. ^{[2
]}

Hadd, Andrew G. ^{[2
]}

机构：

[1] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA

[2] Asuragen Inc, Austin, TX USA

[3] Emory Univ, Sch Med, Atlanta, GA USA

[4] Rush Univ, Med Ctr, Chicago, IL 60612 USA

[5] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA

[6] Integrated Genet Inc, Westborough, MA USA

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2013年 / 161A卷 / 04期

基金：

美国国家卫生研究院;

关键词：

fragile X; FMR1; trinucleotide repeat instability; CGG REPEAT; FMR1; GENE; EXPANDED ALLELES; INSTABILITY; PREMUTATION; PREVALENCE; DNA; IDENTIFICATION; EXPANSION; RANGE;

D O I：

10.1002/ajmg.a.35833

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We investigated the effect of AGG interruptions on fragile X repeat instability upon transmission of fragile X intermediate and small premutation alleles with 4569 CGG repeats. The FMR1 repeat structure was determined for 375 mothers, 48 fathers, and 538 offspring (457 maternal and 81 paternal transmissions) using a novel PCR assay to determine repeat length and AGG interruptions. The number of AGG interruptions and the length of uninterrupted CGG repeats at the 3 end were correlated with repeat instability on transmission. Maternal alleles with no AGGs conferred the greatest risk for unstable transmissions. All nine full mutation expansions were inherited from maternal alleles with no AGGs. Furthermore, the magnitude of repeat expansion was larger for alleles lacking AGG interruptions. Transmissions from paternal alleles with no AGGs also exhibited greater instability than those with one or more AGGs. Our results demonstrate that characterization of the AGG structure within the FMR1 repeat allows more accurate risk estimates of repeat instability and expansion to full mutations for intermediate and small premutation alleles. (c) 2013 Wiley Periodicals, Inc.

引用

页码：771 / 778

页数：8

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