Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report.
Cryptic FMR1 mosaic deletion in a phenotypically normal mother of a boy with fragile X syndrome: case report.
复制标题
DOI：
10.1186/s12881-014-0125-2
复制
发表时间：
2014-11-25
影响因子：
--
通讯作者：
Duan R
中科院分区：
文献类型：
--
作者：
Luo S;Huang W;Xia Q;Xia Y;Du Q;Wu L;Duan R
越来越多的马赛克突变和缺失病例报告使临床医生和遗传学家有了更准确、更集中的产前诊断。由于嵌合现象意味着复发风险的显著增加，详细的亲本分析对风险评估至关重要。我们在这里描述了一位临床未受影响的母亲，她的儿子患有脆性X综合征（FXS），这是由包括整个FMR1的大缺失引起的。为了评估她第二次怀孕的复发风险，进行了一系列基因检测以确定这位母亲的状况。常规单核苷酸多态性（SNP）阵列和荧光原位杂交（FISH）分析在她的血液中检测到两个正常的FMR1拷贝。然而，对缺失区域的深入研究显示，她的体细胞组织中马赛克缺失的比例各不相同：血液中马赛克缺失的比例最低，皮肤、尿液沉积物和月经分泌物中马赛克缺失的比例略高，眉毛中马赛克缺失的比例最高。进一步的FISH分析证实她皮肤来源的成纤维细胞嵌合率为13%。据我们所知，这是第一例因FMR1缺失而嵌合的女性病例，对其嵌合状态的广泛调查为其生殖选择提供了有价值的信息。我们的病例报告也可能提醒临床医生和遗传学家，在有临床定义的“新生”突变的孩子的家庭中，应该仔细考虑具有体细胞异质性的隐性镶嵌现象，以避免第二次怀孕具有相同的遗传异常。
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. 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%. 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.
登录
查看更多内容
影响因子：
1.9
作者：
Kousoulidou, Ludmila;Tanteles, George;Anastasiadou, Violetta
通讯作者：
Anastasiadou, Violetta
影响因子：
2
作者：
Nimmakayalu, Manjunath;Horton, V. Kim;Shchelochkov, Oleg A.
通讯作者：
Shchelochkov, Oleg A.
影响因子：
3.9
作者：
Szuhai, Karoly;Jennes, Ivy;Hogendoorn, Pancras C. W.
通讯作者：
Hogendoorn, Pancras C. W.
影响因子：
30.8
作者：
GEDEON, AK;BAKER, E;MULLEY, JC
通讯作者：
MULLEY, JC
影响因子：
5.3
作者：
Wolff, DJ;Gustashaw, KM;Willard, HF
通讯作者：
Willard, HF