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Instability of TCF4 Triplet Repeat Expansion With Parent–Child Transmission in Fuchs' Endothelial Corneal Dystrophy
| Content Provider | Semantic Scholar |
|---|---|
| Author | Saade, Joanna S. Xing, Chao Gong, Xin Zhi Zhou, Zhengyang Mootha, Venkatesh |
| Copyright Year | 2018 |
| Abstract | 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 (P = 5.9 x 10^-3). A tendency for contraction was seen in transmission of large alleles (repeat length > 120), whereas intermediate alleles (repeat length between 77 and 120) had predilection for further expansion (P = 1.3 x 10^ - 3). Although we noted increased KG severity in the offspring in three pairs, none of these transmissions were associated with allele instability. Conclusions We observed instability of the TCF4 triplet repeat expansion in nearly a third of parent-child transmissions. Large mutant CTG18.1 alleles are prone to contraction, whereas intermediate mutant alleles tend to expand when unstably transmitted. Intergenerational instability of TCF4 repeat expansion has implications on FECD disease inheritance. |
| Starting Page | 4065 |
| Ending Page | 4070 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.arvojournals.org/data/journals/iovs/937431/i1552-5783-59-10-4065.pdf?resultclick=1 |
| Alternate Webpage(s) | https://arvojournals.org/data/journals/iovs/937431/i1552-5783-59-10-4065.pdf?resultclick=1 |
| PubMed reference number | 30098193 |
| Alternate Webpage(s) | https://doi.org/10.1167/iovs.18-24119 |
| DOI | 10.1167/iovs.18-24119 |
| Journal | Investigative ophthalmology & visual science |
| Volume Number | 59 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | ANK Repeat Domains Alleles Corneal dystrophy Histopathologic Grade Neoplasm Grading Polymorphic Microsatellite Marker Analysis Short Tandem Repeat TCF7L2 wt Allele Tandem Repeat Sequences Trinucleotide Repeats Unstable Medical Device Problem disease transmission |
| Content Type | Text |
| Resource Type | Article |
