| Title | Mosaicism and incomplete penetrance of PCDH19 mutations |
| Authors | Liu, Aijie Yang, Xiaoxu Yang, Xiaoling Wu, Qixi Zhang, Jing Sun, Dan Yang, Zhixian Jiang, Yuwu Wu, Xiru Wei, Liping Zhang, Yuehua |
| Affiliation | Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China Capital Inst Pediat, Dept Pediat Neurol, Beijing, Peoples R China Peking Univ, Sch Life Sci, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China Peking Univ, Sch Life Sci, Beijing, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China Wuhan Childrens Hosp, Dept Neurol, Wuhan, Hubei, Peoples R China |
| Issue Date | 2019 |
| Publisher | JOURNAL OF MEDICAL GENETICS |
| Abstract | Background Mutations in the PCDH19 gene have mainly been reported in female patients with epilepsy. To date, PCDH19 mutations have been reported in hundreds of females and only in 10 mosaic male epileptic patients with mosaicism. Objective We aimed to investigate the occurrence of mosaic PCDH19 mutations in 42 families comprising at least one patient with PCDH19-related epilepsy. Methods T wo male patients with mosaic PCDH19 variants were identified using targeted next-generation sequencing. Forty female patients with PCDH19 variants were identified by Sanger sequencing and Multiple Ligation Probe Amplification (MLPA). Microdroplet digital PCR was used to quantify the mutant allelic fractions (MAFs) in 20 families with PCDH19 variants. Results Five mosaic individuals, four males and one female, were identified in total. Mosaic variant was confirmed in multiple somatic tissues from one male patient and in blood from the other male patient. Among 22 female patients harbouring a newly occurred PCDH19 variant identified by Sanger sequencing and MLPA, Sanger sequencing revealed two mosaic fathers (9%, 2/22), one with two affected daughters and the other with an affected child. Two asymptomatic mosaic fathers were confirmed as gonosomal mosaicism, with MAFs ranging from 4.16% to 37.38% and from 1.27% to 19.13%, respectively. In 11 families with apparent de novo variants, 1 female patient was identified as a mosaic with a blood MAF of 26.72%. Conclusion Our study provides new insights into phenotype-genotype correlations in PCDH19 related epilepsy and the finding of high-frequency mosaicism has important implications for genetic counselling. |
| URI | http://hdl.handle.net/20.500.11897/550850 |
| ISSN | 0022-2593 |
| DOI | 10.1136/jmedgenet-2017-105235 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 第一医院 生命科学学院 |
