Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation.

Abstract

Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegia, retinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations. DDHD1 encodes a phospholipase A1, which is involved in the remodelling of phospholipids. We previously described a relatively pure hereditary spastic paraplegia (HSP) phenotype associated with mutations in DDHD1. Here we report a complex form of HSP associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation (NBIA) on brain MRI, due to a novel homozygous mutation in DDHD1. This observation enlarges the clinical spectrum of DDHD1-associated disorders and sheds light on a new aetiology for syndromes associating retinopathy and NBIA. It also emphasizes the role of complex lipids in the retina.

• Authors: Rodolphe Dard, Claire Meyniel, Valérie Touitou, Giovanni Stevanin, Foudil Lamari, Alexandra Durr, Claire Ewenczyk, Fanny Mochel
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 60 Issue 12 Pg. 639-642 (Dec 2017) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 28818478 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Phospholipases A1

Topics

• Brain (diagnostic imaging)
• Homozygote
• Humans
• Iron Metabolism Disorders (diagnosis, genetics)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Mutation
• Neuroaxonal Dystrophies (diagnosis, genetics)
• Optic Atrophies, Hereditary (diagnosis, genetics)
• Phospholipases A1 (genetics)
• Spastic Paraplegia, Hereditary (diagnosis, genetics)
• Syndrome