Work

ALDH1A2‐related disorder: A new genetic syndrome due to alteration of the retinoic acid pathway

Year: 2022

Type: article

Abstract: Aldehyde Dehydrogenase 1, Family Member A2 (ALDH1A2) is essential for the synthesis of retinoic acid from vitamin A. Studies in model organisms demonstrate a critical role for ALDH1A2 in embryonic development, yet few pathogenic variants are linked to congenital anomalies in humans. We present three siblings with multiple congenital anomaly syndrome linked to biallelic sequence variants in ALDH1A2. The major congenital malformations affecting these children include tetralogy of Fallot, absent thymus, diaphragmatic eventration, and talipes equinovarus. Upper airway anomalies, hypocalcemia, and dysmorphic features are newly reported in this manuscript. In vitro functional validation of variants indicated that substitutions reduced the expression of the enzyme. Our clinical and functional data adds to a recent report of biallelic ALDH1A2 pathogenic variants in two families with a similar constellation of congenital malformations. These findings provide further evidence for an autosomal recessive ALDH1A2-deficient recognizable malformation syndrome involving the diaphragm, cardiac and musculoskeletal systems.

Source: American Journal of Medical Genetics Part A

DOI: 10.1002/ajmg.a.62991

Authors: Eyby Leon, Claris Nde, Randall S. Ray, Diego Preciado, Irene E. Zohn

Institution: Children's National

Language: English

Topic: Congenital limb and hand anomalies

Subfield: Developmental Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Eunice Kennedy Shriver National Institute of Child Health and Human Development