» Articles » PMID: 9382110

Deletion of All CGG Repeats Plus Flanking Sequences in FMR1 Does Not Abolish Gene Expression

Overview
Journal Am J Hum Genet
Publisher Cell Press
Specialty Genetics
Date 1997 Oct 23
PMID 9382110
Citations 16
Authors
Affiliations
Soon will be listed here.
Abstract

The fragile X syndrome is due to the new class of dynamic mutations. It is associated with an expansion of a trinucleotide repeat (CGG) in exon 1 of the fragile X mental retardation gene 1 gene (FMR1). Here we present a fragile X family with an unique female patient who was rendered hemizygous for the FRAXA locus due to a large deletion of one X chromosome. In addition, the other X had a microdeletion in FMR1. PCR and sequence analysis revealed that the microdeletion included all CGG repeats plus 97 bp of flanking sequences, leaving transcription start site and translation start site intact. Despite this total lack of CGG repeats in the FMR1 gene, Western blot analysis showed expression of FMRP, and the patient's phenotype was essentially normal. X-inactivation studies of the androgen-receptor (AR) locus and haplotype determination of microsatellite markers gave evidence that the deletion probably originated from regression of a fully mutated FMR1 gene. Although the minimal number of CGG repeats hitherto reported in FRAXA is six, and at least four other genes associated with CGG repeats are known, suggesting an as yet unknown function of these repeats, our study clearly demonstrates that the absence of CGG repeats does not abolish expression of the FMR1 gene in lymphoblastoid cells.

Citing Articles

Somatic Instability Leading to Mosaicism in Fragile X Syndrome and Associated Disorders: Complex Mechanisms, Diagnostics, and Clinical Relevance.

Protic D, Polli R, Bettella E, Usdin K, Murgia A, Tassone F Int J Mol Sci. 2025; 25(24.

PMID: 39769443 PMC: 11728179. DOI: 10.3390/ijms252413681.


Intersection of the fragile X-related disorders and the DNA damage response.

Kumari D, Grant-Bier J, Kadyrov F, Usdin K DNA Repair (Amst). 2024; 144:103785.

PMID: 39549538 PMC: 11789500. DOI: 10.1016/j.dnarep.2024.103785.


CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.

Sirois C, Guo Y, Li M, Wolkoff N, Korabelnikov T, Sandoval S Cell Rep. 2024; 43(6):114330.

PMID: 38865241 PMC: 11240841. DOI: 10.1016/j.celrep.2024.114330.


Unravelling the link between neurodevelopmental disorders and short tandem CGG-repeat expansions.

Annear D, Kooy R Emerg Top Life Sci. 2023; 7(3):265-275.

PMID: 37768318 PMC: 10754333. DOI: 10.1042/ETLS20230021.


Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants in and Associated Phenotypes.

Tekendo-Ngongang C, Grochowsky A, Solomon B, Yano S Genes (Basel). 2021; 12(11).

PMID: 34828275 PMC: 8623550. DOI: 10.3390/genes12111669.


References
1.
Tarleton J, RICHIE R, Schwartz C, Rao K, Aylsworth A, Lachiewicz A . An extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype. Hum Mol Genet. 1993; 2(11):1973-4. DOI: 10.1093/hmg/2.11.1973. View

2.
Malter H, Iber J, Willemsen R, de Graaff E, Tarleton J, Leisti J . Characterization of the full fragile X syndrome mutation in fetal gametes. Nat Genet. 1997; 15(2):165-9. DOI: 10.1038/ng0297-165. View

3.
Nancarrow J, Kremer E, Holman K, Eyre H, Doggett N, Le Paslier D . Implications of FRA16A structure for the mechanism of chromosomal fragile site genesis. Science. 1994; 264(5167):1938-41. DOI: 10.1126/science.8009225. View

4.
Geerkens C, Just W, Vogel W . Deletions of Xq and growth deficit: a review. Am J Med Genet. 1994; 50(2):105-13. DOI: 10.1002/ajmg.1320500202. View

5.
Meijer H, de Graaff E, Merckx D, Jongbloed R, de Die-Smulders C, Engelen J . A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome. Hum Mol Genet. 1994; 3(4):615-20. DOI: 10.1093/hmg/3.4.615. View