An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene

Franklin Quan, Jonathan (Jon) Zonana, Kristine Gunter, Kristine L. Peterson, R. Ellen Magenis, Bradley W. Popovich

Research output: Contribution to journalArticle

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Abstract

Fragile X syndrome is the most common form of inherited mental retardation and results from the transcriptional inactivation of the FMR1 gene. In the vast majority of cases, this is caused by the expansion of an unstable CGG repeat in the first exon of the FMR1 gene. We describe here a phenotypically atypical case of fragile X syndrome, caused by a deletion that includes the entire FMR1 gene and ≥9.0 Mb of flanking DNA. The proband, RK, was a 6-year-old mentally retarded male with obesity and anal atresia. A diagnosis of fragile X syndrome was established by the failure of RK's DNA to hybridize to a 558-bp PstI-XhoI fragment (pfxa3) specific for the 5′-end of the FMR1 gene. The analysis of flanking markers in the interval from Xq26.3-q28 indicated a deletion extending from between 160-500 kb distal and 9.0 Mb proximal to the FMR1 gene. High-resolution chromosome banding confirmed a deletion with breakpoints in Xq26.3 and Xq27.3. This deletion was maternally transmitted and arose as a new mutation on the grandpaternal X chromosome. The maternal transmission of the deletion was confirmed by FISH using a 34-kb cosmid (c31.4) containing most of the FMR1 gene. These results indicated that RK carried a deletion of the FMR1 region with the most proximal breakpoint described to date. This patient's unusual clinical presentation may indicate the presence of genes located in the deleted interval proximal to the FMR1 locus that are able to modify the fragile X syndrome phenotype.

Original languageEnglish (US)
Pages (from-to)1042-1051
Number of pages10
JournalAmerican Journal of Human Genetics
Volume56
Issue number5
StatePublished - May 1995

Fingerprint

Fragile X Syndrome
Genes
Chromosome Banding
Imperforate Anus
Cosmids
DNA
Mentally Disabled Persons
X Chromosome
Gene Silencing
Intellectual Disability
Exons
Obesity
Mothers
Phenotype
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Quan, F., Zonana, J. J., Gunter, K., Peterson, K. L., Magenis, R. E., & Popovich, B. W. (1995). An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. American Journal of Human Genetics, 56(5), 1042-1051.

An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. / Quan, Franklin; Zonana, Jonathan (Jon); Gunter, Kristine; Peterson, Kristine L.; Magenis, R. Ellen; Popovich, Bradley W.

In: American Journal of Human Genetics, Vol. 56, No. 5, 05.1995, p. 1042-1051.

Research output: Contribution to journalArticle

Quan, F, Zonana, JJ, Gunter, K, Peterson, KL, Magenis, RE & Popovich, BW 1995, 'An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene', American Journal of Human Genetics, vol. 56, no. 5, pp. 1042-1051.
Quan, Franklin ; Zonana, Jonathan (Jon) ; Gunter, Kristine ; Peterson, Kristine L. ; Magenis, R. Ellen ; Popovich, Bradley W. / An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. In: American Journal of Human Genetics. 1995 ; Vol. 56, No. 5. pp. 1042-1051.
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