title: Germinal mosaicism for a deletion of the FMR1 gene leading to fragile X syndrome.
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.
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA; Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakornpathom, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Jiraanont
authors.affiliation: Department of Pediatrics, University of California Davis, Davis, CA, USA; MIND Institute, School of Medicine, University of California Davis, Davis, CA, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Institute of Medical Genetics, Catholic University of the Sacred Heart-Agostino Gemelli University Hospital, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Neri
authors.affiliation: Institute of Medical Genetics, Catholic University of the Sacred Heart-Agostino Gemelli University Hospital, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zollino
authors.affiliation: Institute of Medical Genetics, Catholic University of the Sacred Heart-Agostino Gemelli University Hospital, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Murdolo
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA; MIND Institute, School of Medicine, University of California Davis, Davis, CA, USA. Electronic address: ftassone@ucdavis.edu.
authors.forename: F
authors.initials: F
authors.lastname: Tassone
mesh_terms: D002648:Child; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics*; D017353:Gene Deletion; D005817:Genetic Counseling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism; D011247:Pregnancy; D011296:Prenatal Diagnosis; D020280:Sertraline / Q000627:therapeutic use
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D020280:Sertraline; C497683:FMR1 protein, human
keywords: FMR1 gene; Fragile X; Germinal mosaicism; Large deletions