Science Foundation (31530041). The work of H.L. was supported by Ningbo Health Branding
Subject Fund (PPXK2018-06).
Author contributions P.T., J.S., Z.W., S.W., J.W. and W.L. contributed equally. H.P., R.B., J.Z., Y.W.
and P.Y.L. contributed equally. Q.Z., J.Y., X.W. and X.Y. designed the study, directed and supervised
the research. P.T., J.S., Z.W., S.W., J.W., W.L. and H.P. performed experiments and analysed most of
the data. J.Z., Y.W., P.Y.L., R.F., H.H., Z.Y., X.H. and Y.Z. performed experiments. J.S., R.B., W.Y., Q.Z.,
J.H., W.W., B.S., M.Y., D.L., H.L., D.D., K.H., K.M., C.R., J.M., R.M.L. and X.W. enrolled the patients,
collected and interpreted clinical information. N.D. provided comments. Q.Z., J.Y., X.Y. and P.T.
wrote the manuscript, with input from others. I.A. provided valuable advice and edited the
manuscript. All authors contributed to the review and approval of the manuscript.
Competing interests J.Y. is a consultant of Denali Therapeutics. R.B., K.H. and K.M. are
employees of GeneDx, Inc. The rest of authors declare no competing financial interests.Additional information
Supplementary information is available for this paper at https://doi.org/10.1038/s41586-019-
1830-y.
Correspondence and requests for materials should be addressed to X.Y., X.W., J.Y. or Q.Z.
Peer review information Nature thanks Min Ae Lee-Kirsch, Egil Lien and the other, anonymous,
reviewer(s) for their contribution to the peer review of this work.
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