title: Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report.
abstract: BACKGROUND
  Increasing number of case reports of mosaic mutations and deletions have better armed clinicians and geneticists with more accurate and focused prenatal diagnoses. Since mosaicism means a significant increase of recurrence risk, detailed parental profiling is essential for risk assessments.
  
  
  METHODS
  We here describe a clinically unaffected mother with a son who had fragile X syndrome (FXS) caused by a large deletion that includes the entire FMR1. To assess the recurrence risk regarding her second pregnancy, a series of genetic tests were conducted to establish this mother's status. Routine single nucleotide polymorphism (SNP) array and fluorescence in situ hybridisation (FISH) analyses detected two normal FMR1 copies in her blood. However, in-depth studies across the deleted region revealed varying proportions of mosaic deletion in her somatic tissues: lowest in the blood, moderately higher in the skin, urine sediment and menstrual discharge and highest in her eyebrow. Further FISH analysis of her skin-derived fibroblasts confirmed mosaicism of 13%.
  
  
  CONCLUSIONS
  To our knowledge, this is the first characterized case of a female who was mosaic for an FMR1 deletion and extensive investigation of her mosaic status provided valuable information for her reproduction choices. Our case report may also alert clinicians and geneticists that a cryptic mosaicism with somatic heterogeneity should be carefully considered in families with children having clinically defined 'de novo' mutations, to avoid a second pregnancy with identical genetic abnormalities.
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. luoshiyu@sklmg.edu.cn.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Luo
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. huangwen@sklmg.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. xiaqiuping@sklmg.edu.cn.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. xiayan@sklmg.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. duqian@sklmg.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. wulingqian@sklmg.edu.cn.
authors.forename: Lingqian
authors.initials: L
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, 410078, Hunan, China. duanranhui@sklmg.edu.cn.
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
mesh_terms: D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000097:blood / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008297:Male; D009030:Mosaicism; D009035:Mothers; D010641:Phenotype; D017384:Sequence Deletion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human