Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases.
Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases.
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DOI：
10.1002/humu.23281
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发表时间：
2017-10
期刊：
影响因子：
3.9
通讯作者：
Goriely A
中科院分区：
文献类型：
--
作者：
Bernkopf M;Hunt D;Koelling N;Morgan T;Collins AL;Fairhurst J;Robertson SP;Douglas AGL;Goriely A
我们报告了一例Larsen综合征的男性患者，发现FLNB的一个新的点突变是马赛克的，这可能为未来后代的传播风险提供基于证据的个性化咨询。通过双脱氧测序，在口腔黏膜和成纤维细胞DNA中检测到编码p.（Tyr233Cys）突变的低水平FLNB c.698A>G。突变定量是通过从三种体细胞组织（血液、成纤维细胞、唾液）和精子样本中提取DNA的深度下一代测序（NGS）进行的。该突变在所有测试组织中均可检测到，水平在7%至10%之间（突变存在于约20%的二倍体体细胞和7%的单倍体精子中），表明该患者涉及体细胞和性腺谱系。本报告阐述了对患有花叶病的男性精子进行有针对性的NGS分析的临床应用，以提供个性化的传播风险，并提供基于证据的生殖安全咨询。
We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence‐based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low‐level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next‐generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in ∼20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence‐based counseling on reproductive safety.
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影响因子：
3.9
作者：
Farrington-Rock, Claire;Firestein, Marc H.;Krakow, Deborah
通讯作者：
Krakow, Deborah
影响因子：
0.7
作者：
Frints, SGM;De Smet, L;Fryns, JP
通讯作者：
Fryns, JP
DOI：
10.1002/ajmg.1320470212
发表时间：
1993-08-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
PETRELLA, R;RABINOWITZ, JG;HIRSCHHORN, K
通讯作者：
HIRSCHHORN, K
影响因子：
3
作者：
Winer, N.;Kyndt, F.;Le Caignec, C.
通讯作者：
Le Caignec, C.
影响因子：
30.8
作者：
Krakow, D;Robertson, SP;Cohn, DH
通讯作者：
Cohn, DH