Identification and characterization of short-chain dehydrogenase/reductase 3 (DHRS3) deficiency, a retinoic acid embryopathy of humans.

ABSTRACT:

Purpose

Signaling by the morphogen all-trans retinoic acid (RA) is critical for embryonic development, during which its tissue concentration must be tightly regulated. We investigated 8 sibships (12 individuals) segregating 5 different homozygous variants of dehydrogenase/reductase 3 ( DHRS3), which encodes an embryonically expressed enzyme (short-chain dehydrogenase/reductase 3; also termed SDR16C1) that catalyzes the reduction of retinaldehyde to retinol, limiting excessive RA synthesis.

Methods

We assessed variant pathogenicity using comparative phenotypic and bioinformatic analysis, quantification of DHRS3 expression, and measurement of plasma retinoid metabolites.

Results

Five homozygotes from 3 families (1 family segregating a deletion of th

SUBMITTER: Hashimoto AS 

PROVIDER: S-EPMC12167057 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature