Germinal mosaicism for a deletion of the FMR1 gene leading to fragile X syndrome

P. Jiraanont, Randi J Hagerman, G. Neri, M. Zollino, M. Murdolo, Flora Tassone

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aberrant CGG trinucleotide amplification within the FMR1 gene, which spans approximately 38 Kb of genomic DNA is almost always what leads to fragile X syndrome (FXS). However, deletions of part or the entire FMR1 gene can also cause FXS. Both CGG amplification-induced silencing and deletions result in the absence of the FMR1 gene product, FMRP. Here, we report a rare case of germinal mosaicism of a deletion encompassing approximately 300 Kb of DNA, which by removing the entire FMR1 gene led to FXS. The male proband, carrying the deletion, presented in clinic with the typical features of FXS. His mother was analyzed by FISH on metaphase chromosomes with cosmid probe c22.3 spanning the FMR1 locus, and she was found not to carry the deletion on 30 analyzed cells from peripheral blood lymphocytes. Prenatal examination of the mother's third pregnancy showed that the male fetus also had the same deletion as the proband. Following this prenatal diagnosis, FISH analysis in the mother was expanded to 400 metaphases from peripheral lymphocytes, and a heterozygous FMR1 deletion was found in three. Although this result could be considered questionable from a diagnostic point of view, it indicates that the deletion is in the ovary's germinal cells.

Original languageEnglish (US)
Pages (from-to)459-462
Number of pages4
JournalEuropean Journal of Medical Genetics
Volume59
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Fragile X Syndrome
Mosaicism
Gene Deletion
Metaphase
Genes
Lymphocytes
Cosmids
DNA
Prenatal Diagnosis
Ovary
Blood Cells
Fetus
Chromosomes
Pregnancy

Keywords

  • FMR1 gene
  • Fragile X
  • Germinal mosaicism
  • Large deletions

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Germinal mosaicism for a deletion of the FMR1 gene leading to fragile X syndrome. / Jiraanont, P.; Hagerman, Randi J; Neri, G.; Zollino, M.; Murdolo, M.; Tassone, Flora.

In: European Journal of Medical Genetics, Vol. 59, No. 9, 01.09.2016, p. 459-462.

Research output: Contribution to journalArticle

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