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

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• 作者：Shiyu Luo ; Wen Huang ; Qiuping Xia ; Yan Xia ; Qian Du ; Lingqian Wu…
• 关键词：Deletion ; Fragile X syndrome ; Mosaic ; Somatic heterogeneity
• 刊名：BMC Medical Genetics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：15
• 期：1
• 全文大小：1,373 KB
• 参考文献：1. Oostra, BA, Chiurazzi, P (2001) The fragile X gene and its function. Clin Genet 60: pp. 399-408 CrossRef
  2. Coffee, B, Ikeda, M, Budimirovic, DB, Hjelm, LN, Kaufmann, WE, Warren, ST (2008) Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am J Med Genet A 146A: pp. 1358-1367 CrossRef
  3. Hammond, LS, Macias, MM, Tarleton, JC, Shashidhar Pai, G (1997) Fragile X syndrome and deletions in FMR1: new case and review of the literature. Am J Med Genet 72: pp. 430-434 CrossRef
  4. Szuhai, K, Jennes, I, Jong, D, Bovée, JV, Wiweger, M, Wuyts, W, Hogendoorn, PC (2011) Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients. Hum Mutat 32: pp. E2036-E2049 CrossRef
  5. Kousoulidou, L, Tanteles, G, Moutafi, M, Sismani, C, Patsalis, PC, Anastasiadou, V (2013) 263.4?kb deletion within the TCF4 gene consistent with Pitt-Hopkins syndrome, inherited from a mosaic parent with normal phenotype. Eur J Med Genet 56: pp. 314-318 CrossRef
  6. Nimmakayalu, M, Horton, VK, Darbro, B, Patil, SR, Alsayouf, H, Keppler-Noreuil, K, Shchelochkov, OA (2013) Apparent germline mosaicism for a novel 19p13.13 deletion disrupting NFIX and CACNA1A. Am J Med Genet A 161: pp. 1105-1109 CrossRef
  7. Luo S, Huang W, Xia Q, Du Q, Wu L, Duan R: Mutational analyses of the FMR1 gene in chinese pediatric population of fragile X suspects: low tolerance for point mutation. / J Child Neurol. in press.
  8. Gedeon, AK, Baker, E, Robinson, H, Partington, MW, Gross, B, Manca, A, Korn, B, Poustka, A, Yu, S, Sutherland, GR, Mulley, JC (1992) Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat Genet 1: pp. 341-344 CrossRef
  9. Nagamani, SC, Erez, A, Probst, FJ, Bader, P, Evans, P, Baker, LA, Fang, P, Bertin, T, Hixson, P, Stankiewicz, P, Nelson, D, Patel, A, Cheung, SW (2012) Small genomic rearrangements involving FMR1 support the importance of its gene dosage for normal neurocognitive function. Neurogenetics 13: pp. 333-339 CrossRef
  10. Wolff, DJ, Gustashaw, KM, Zurcher, V, Ko, L, White, W, Weiss, L, Dyke, DL, Schwartz, S, Willard, HF (1997) Deletions in Xq26.3-q27.3 including FMR1 result in a severe phenotype in a male and variable phenotypes in females depending upon the X inactivation pattern. Hum Genet 100: pp. 256-261 CrossRef
  11. Carlson, BM (2013) Human Embryology & Developmental Biology. W.B. Saunders Co, Philadelphia, PA
  
• 刊物主题：Human Genetics; Genetics and Population Dynamics;
• 出版者：BioMed Central
• ISSN：1471-2350

文摘

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.