Instability of TCF4 Triplet Repeat Expansion With Parent-Child Transmission in Fuchs' Endothelial Corneal Dystrophy.
Instability of TCF4 Triplet Repeat Expansion With Parent-Child Transmission in Fuchs' Endothelial Corneal Dystrophy.
复制标题
Fuchs 内皮性角膜营养不良中 TCF4 三联体重复扩增与亲子传递的不稳定性。
DOI：
10.1167/iovs.18-24119
复制
发表时间：
2018
影响因子：
4.4
通讯作者：
Mootha,VVinod
中科院分区：
文献类型：
--
作者：
Saade,JoannaS;Xing,Chao;Gong,Xin;Zhou,Zhengyang;Mootha,VVinod
Purpose: Fuchs' endothelial corneal dystrophy (FECD) caused by the CTG triplet repeat expansion in the TCF4 gene (CTG18. 1 locus) is the most common repeat expansion disorder. Intergenerational instability of expanded repeats and clinical anticipation are hallmarks of other repeat expansion disorders. In this study, we examine stability of triplet repeat allele length and FECD disease severity in parent–child transmission of the expanded CTG18. 1 allele.Methods: We studied 44 parent–child transmissions of the mutant expanded CTG18. 1 allele from 26 FECD families. The CTG18. 1 polymorphism was genotyped using short tandem repeat analysis, triplet repeat primed PCR assay, and Southern blot analysis. FECD severity was assessed using modified Krachmer grading (KG) system. Triplet repeat length of mutant allele and KG severity were compared between generations.Results: Instability of the expanded allele was seen in 14 of 44 (31.8%) parent–child transmissions, and the likelihood of an unstable event increased with the size of the parental allele (Display Formula\(\def\upalpha {\unicode [Times]{x3B1}}\)\(\def\upbeta {\unicode [Times]{x3B2}}\)\(\def\upgamma {\unicode [Times]{x3B3}}\)\(\def\updelta {\unicode [Times]{x3B4}}\)\(\def\upvarepsilon {\unicode [Times]{x3B5}}\)\(\def\upzeta {\unicode [Times]{x3B6}}\)\(\def\upeta {\unicode [Times]{x3B7}}\)\(\def\uptheta {\unicode [Times]{x3B8}}\)\(\def\upiota {\unicode [Times]{x3B9}}\)\(\def\upkappa {\unicode [Times]{x3BA}}\)\(\def\uplambda {\unicode [Times]{x3BB}}\)\(\def\upmu {\unicode [Times]{x3BC}}\)\(\def\upnu {\unicode [Times]{x3BD}}\)\(\def\upxi {\unicode [Times]{x3BE}}\)\(\def\upomicron {\unicode [Times]{x3BF}}\)\(\def\uppi {\unicode [Times]{x3C0}}\)\(\def\uprho {\unicode [Times]{x3C1}}\)\(\def\upsigma {\unicode [Times]{x3C3}}\)\(\def\uptau {\unicode [Times]{x3C4}}\)\(\def\upupsilon {\unicode [Times]{x3C5}}\)\(\def\upphi {\unicode [Times]{x3C6}}\)\(\def\upchi {\unicode [Times]{x3C7}}\)\(\def\uppsy {\unicode [Times]{x3C8}}\)\(\def\upomega {\unicode [Times]{x3C9}}\)\(\def\bialpha {\boldsymbol {\alpha}}\)\(\def\bibeta {\boldsymbol {\beta}}\)\(\def\bigamma {\boldsymbol {\gamma}}\)\(\def\bidelta {\boldsymbol {\delta}}\)\(\def\bivarepsilon {\boldsymbol {\varepsilon}}\)\(\def\bizeta {\boldsymbol {\zeta}}\)\(\def\bieta {\boldsymbol {\eta}}\)\(\def\bitheta {\boldsymbol {\theta}}\)\(\def\biiota {\boldsymbol {\iota}}\)\(\def\bikappa {\boldsymbol {\kappa}}\)\(\def\bilambda {\boldsymbol {\lambda}}\)\(\def\bimu {\boldsymbol {\mu}}\)\(\def\binu {\boldsymbol {\nu}}\)\(\def\bixi {\boldsymbol {\xi}}\)\(\def\biomicron {\boldsymbol {\micron}}\)\(\def\bipi {\boldsymbol {\pi}}\)\(\def\birho {\boldsymbol {\rho}}\)\(\def\bisigma {\boldsymbol {\sigma}}\)\(\def\bitau {\boldsymbol {\tau}}\)\(\def\biupsilon {\boldsymbol {\upsilon}}\)\(\def\biphi {\boldsymbol {\phi}}\)\(\def\bichi {\boldsymbol {\chi}}\)\(\def\bipsy {\boldsymbol {\psy}}\)\(\def\biomega {\boldsymbol {\omega}}\)\(\def\bupalpha {\unicode [Times]{x1D6C2}}\)\(\def\bupbeta {\unicode [Times]{x1D6C3}}\)\(\def\bupgamma {\unicode [Times]{x1D6C4}}\)\(\def\bupdelta {\unicode [Times]{x1D6C5}}\)\(\def\bupepsilon {\unicode [Times]{x1D6C6}}\)\(\def\bupvarepsilon {\unicode [Times]{x1D6DC}}\)\(\def\bupzeta {\unicode [Times]{x1D6C7}}\)\(\def\bupeta {\unicode [Times]{x1D6C8}}\)\(\def\buptheta {\unicode [Times]{x1D6C9}}\)\(\def\bupiota
Purpose: Fuchs' endothelial corneal dystrophy (FECD) caused by the CTG triplet repeat expansion in the TCF4 gene (CTG18. 1 locus) is the most common repeat expansion disorder. Intergenerational instability of expanded repeats and clinical anticipation are hallmarks of other repeat expansion disorders. In this study, we examine stability of triplet repeat allele length and FECD disease severity in parent–child transmission of the expanded CTG18. 1 allele.Methods: We studied 44 parent–child transmissions of the mutant expanded CTG18. 1 allele from 26 FECD families. The CTG18. 1 polymorphism was genotyped using short tandem repeat analysis, triplet repeat primed PCR assay, and Southern blot analysis. FECD severity was assessed using modified Krachmer grading (KG) system. Triplet repeat length of mutant allele and KG severity were compared between generations.Results: Instability of the expanded allele was seen in 14 of 44 (31.8%) parent–child transmissions, and the likelihood of an unstable event increased with the size of the parental allele (Display Formula\(\def\upalpha {\unicode [Times]{x3B1}}\)\(\def\upbeta {\unicode [Times]{x3B2}}\)\(\def\upgamma {\unicode [Times]{x3B3}}\)\(\def\updelta {\unicode [Times]{x3B4}}\)\(\def\upvarepsilon {\unicode [Times]{x3B5}}\)\(\def\upzeta {\unicode [Times]{x3B6}}\)\(\def\upeta {\unicode [Times]{x3B7}}\)\(\def\uptheta {\unicode [Times]{x3B8}}\)\(\def\upiota {\unicode [Times]{x3B9}}\)\(\def\upkappa {\unicode [Times]{x3BA}}\)\(\def\uplambda {\unicode [Times]{x3BB}}\)\(\def\upmu {\unicode [Times]{x3BC}}\)\(\def\upnu {\unicode [Times]{x3BD}}\)\(\def\upxi {\unicode [Times]{x3BE}}\)\(\def\upomicron {\unicode [Times]{x3BF}}\)\(\def\uppi {\unicode [Times]{x3C0}}\)\(\def\uprho {\unicode [Times]{x3C1}}\)\(\def\upsigma {\unicode [Times]{x3C3}}\)\(\def\uptau {\unicode [Times]{x3C4}}\)\(\def\upupsilon {\unicode [Times]{x3C5}}\)\(\def\upphi {\unicode [Times]{x3C6}}\)\(\def\upchi {\unicode [Times]{x3C7}}\)\(\def\uppsy {\unicode [Times]{x3C8}}\)\(\def\upomega {\unicode [Times]{x3C9}}\)\(\def\bialpha {\boldsymbol {\alpha}}\)\(\def\bibeta {\boldsymbol {\beta}}\)\(\def\bigamma {\boldsymbol {\gamma}}\)\(\def\bidelta {\boldsymbol {\delta}}\)\(\def\bivarepsilon {\boldsymbol {\varepsilon}}\)\(\def\bizeta {\boldsymbol {\zeta}}\)\(\def\bieta {\boldsymbol {\eta}}\)\(\def\bitheta {\boldsymbol {\theta}}\)\(\def\biiota {\boldsymbol {\iota}}\)\(\def\bikappa {\boldsymbol {\kappa}}\)\(\def\bilambda {\boldsymbol {\lambda}}\)\(\def\bimu {\boldsymbol {\mu}}\)\(\def\binu {\boldsymbol {\nu}}\)\(\def\bixi {\boldsymbol {\xi}}\)\(\def\biomicron {\boldsymbol {\micron}}\)\(\def\bipi {\boldsymbol {\pi}}\)\(\def\birho {\boldsymbol {\rho}}\)\(\def\bisigma {\boldsymbol {\sigma}}\)\(\def\bitau {\boldsymbol {\tau}}\)\(\def\biupsilon {\boldsymbol {\upsilon}}\)\(\def\biphi {\boldsymbol {\phi}}\)\(\def\bichi {\boldsymbol {\chi}}\)\(\def\bipsy {\boldsymbol {\psy}}\)\(\def\biomega {\boldsymbol {\omega}}\)\(\def\bupalpha {\unicode [Times]{x1D6C2}}\)\(\def\bupbeta {\unicode [Times]{x1D6C3}}\)\(\def\bupgamma {\unicode [Times]{x1D6C4}}\)\(\def\bupdelta {\unicode [Times]{x1D6C5}}\)\(\def\bupepsilon {\unicode [Times]{x1D6C6}}\)\(\def\bupvarepsilon {\unicode [Times]{x1D6DC}}\)\(\def\bupzeta {\unicode [Times]{x1D6C7}}\)\(\def\bupeta {\unicode [Times]{x1D6C8}}\)\(\def\buptheta {\unicode [Times]{x1D6C9}}\)\(\def\bupiota