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

• Published in: European journal of medical genetics Vol. 60; no. 12; pp. 639 - 642
• Main Authors: Dard, Rodolphe, Meyniel, Claire, Touitou, Valérie, Stevanin, Giovanni, Lamari, Foudil, Durr, Alexandra, Ewenczyk, Claire, Mochel, Fanny
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Masson SAS 01-12-2017
• Subjects: Brain - diagnostic imaging; DDHD1; Hereditary spastic paraplegia; Homozygote; Humans; Iron Metabolism Disorders - diagnosis; Iron Metabolism Disorders - genetics; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; NBIA; Neuroaxonal Dystrophies - diagnosis; Neuroaxonal Dystrophies - genetics; Optic Atrophies, Hereditary - diagnosis; Optic Atrophies, Hereditary - genetics; Phospholipases A1 - genetics; Phospholipids; Retinopathy; Spastic Paraplegia, Hereditary - diagnosis; Spastic Paraplegia, Hereditary - genetics; Syndrome; Hereditary spastic paraplegia; NBIA; Phospholipids; Retinopathy; DDHD1
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2017.08.015

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.