Retrotransposition disrupting EBP in a girl and her mother with X-linked dominant chondrodysplasia punctata.

Takuya Hiraide, Yohei Masunaga, Akira Honda, Fumiko Kato, Tokiko Fukuda, Maki Fukami, Mitsuko Nakashima, Hirotomo Saitsu, Tsutomu Ogata

Journal of human genetics 2022 May

filter terms:

X-linked dominant chondrodysplasia punctata (CDPX2) is a rare congenital disorder caused by pathogenic variants in EBP on Xp11.23. We encountered a girl and her mother with CDPX2-compatible phenotypes including punctiform calcification in the neonatal period of the girl, and asymmetric limb shortening and ichthyosis following the Blaschko lines in both subjects. Although Sanger direct sequencing failed to reveal a disease-causing variant in EBP, whole genome sequencing (WGS) followed by Manta analysis identified a ~ 4.5 kb insertion at EBP exon 2 of both subjects. The insertion was associated with the hallmarks of retrotransposition such as an antisense poly(A) tail, a target site duplication, and a consensus endonuclease cleavage site, and the inserted sequence harbored full-length SVA_F1 element with 5'- and 3'-transductions containing the Alu sequence. The results imply the relevance of retrotransposition to the human genetic diseases and the usefulness of WGS in the identification of retrotransposition. © 2021. The Author(s), under exclusive licence to The Japan Society of Human Genetics.

Citation

Takuya Hiraide, Yohei Masunaga, Akira Honda, Fumiko Kato, Tokiko Fukuda, Maki Fukami, Mitsuko Nakashima, Hirotomo Saitsu, Tsutomu Ogata. Retrotransposition disrupting EBP in a girl and her mother with X-linked dominant chondrodysplasia punctata. Journal of human genetics. 2022 May;67(5):303-306