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Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report

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 assessmen...

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Autores principales: Luo, Shiyu, Huang, Wen, Xia, Qiuping, Xia, Yan, Du, Qian, Wu, Lingqian, Duan, Ranhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411709/
https://www.ncbi.nlm.nih.gov/pubmed/25421229
http://dx.doi.org/10.1186/s12881-014-0125-2
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author Luo, Shiyu
Huang, Wen
Xia, Qiuping
Xia, Yan
Du, Qian
Wu, Lingqian
Duan, Ranhui
author_facet Luo, Shiyu
Huang, Wen
Xia, Qiuping
Xia, Yan
Du, Qian
Wu, Lingqian
Duan, Ranhui
author_sort Luo, Shiyu
collection PubMed
description 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. CASE PRESENTATION: 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%. CONCLUSION: 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.
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spelling pubmed-44117092015-04-29 Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report Luo, Shiyu Huang, Wen Xia, Qiuping Xia, Yan Du, Qian Wu, Lingqian Duan, Ranhui BMC Med Genet Case Report 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. CASE PRESENTATION: 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%. CONCLUSION: 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. BioMed Central 2014-11-25 /pmc/articles/PMC4411709/ /pubmed/25421229 http://dx.doi.org/10.1186/s12881-014-0125-2 Text en © Luo et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Luo, Shiyu
Huang, Wen
Xia, Qiuping
Xia, Yan
Du, Qian
Wu, Lingqian
Duan, Ranhui
Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title_full Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title_fullStr Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title_full_unstemmed Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title_short Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report
title_sort cryptic fmr1 mosaic deletion in a phenotypically normal mother of a boy with fragile x syndrome: case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411709/
https://www.ncbi.nlm.nih.gov/pubmed/25421229
http://dx.doi.org/10.1186/s12881-014-0125-2
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