Diagnostic potential of the amniotic fluid cells transcriptome in deciphering mendelian disease: a proof-of-concept
Mianne Lee, Anna Ka‐Yee Kwong, Martin Man Chun Chui, Jeffrey Fong Ting Chau, Christopher Chun Yu Mak, Sandy Leung–Kuen Au, Hei Man Lo, Kelvin Y.K. Chan, Vicente A. Yépez, Julien Gagneur, Anita Sik Yau Kan, Brian Hon‐Yin Chung
Abstract
RNA sequencing (RNA-seq) is emerging in genetic diagnoses as it provides functional support for the interpretation of variants of uncertain significance. However, the use of amniotic fluid (AF) cells for RNA-seq has not yet been explored. Here, we examined the expression of clinically relevant genes in AF cells (n = 48) compared with whole blood and fibroblasts. The number of well-expressed genes in AF cells was comparable to that in fibroblasts and much higher than that in blood across different disease categories. We found AF cells RNA-seq feasible and beneficial in prenatal diagnosis (n = 4) as transcriptomic data elucidated the molecular consequence leading to the pathogenicity upgrade of variants in CHD7 and COL1A2 and revising the in silico prediction of a variant in MYRF. AF cells RNA-seq could become a reasonable choice for postnatal patients with advantages over fibroblasts and blood as it prevents invasive procedures.