Pseudoxanthoma elasticum with generalized retinal dysfunction, a common finding?
OBJECTIVE
Pseudoxanthoma elasticum (PXE; [MIM 264800]) is an autosomal recessive systemic disorder characterized by progressive degeneration and calcification of elastic fibers in connective tissue. The phenotype is variable, with cutaneous, vascular, and ophthalmic abnormalities. The disorder is a consequence of mutations in the ABCC6 gene. Visual impairment is mainly due to neovascular complications, and retinal function is usually assumed to be normal. The purpose of this study was the objective assessment of macular and generalized retinal function in unrelated patients with clinical and/or genetic features of PXE.


METHODS
Four unrelated patients carrying a clinical diagnosis of PXE presented with unexplained visual loss. After ophthalmic examination, retinal and macular function was assessed by full-field electroretinogram (ERG) and pattern ERG, respectively, according to ISCEV (International Society for Clinical Electrophysiology of Vision) recommendations. Molecular analysis of the ABCC6 gene was performed in three patients by dHPLC (denaturing high-performance liquid chromatography) and direct sequencing.


RESULTS
Full-field ERG revealed significant reduction of cone and rod responses in all four patients. Funduscopic appearances varied. Three patients were found to carry ABCC6 mutations. In case 1, a novel nonsense mutation (p.L1474X) was detected in exon 31 paired with a splice-site mutation. Mutation analyses in cases 3 and 4 revealed previously reported ABCC6 mutations.


CONCLUSIONS
These findings suggest that retinal dysfunction in PXE may not be uncommon. The mechanism underlying retinal dysfunction is unknown but may result from metabolic disturbance leading to retinal toxicity with a possible role of modifying genetic or environmental factors rather than specific ABCC6 mutations.
Audo
Isabelle
I
Laboratoire de Physiopathologie Cellulaire Moléculaire et de la Rétine, Institut National de la Santé et de la Recherche Médicale, Université Pierre et Marie Curie, Paris, France.
Vanakker
Olivier M
OM
Smith
Alaric
A
Leroy
Bart P
BP
Robson
Anthony G
AG
Jenkins
Sharon A
SA
Coucke
Paul J
PJ
Bird
Alan C
AC
De Paepe
Anne
A
Holder
Graham E
GE
Webster
Andrew R
AR
D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D011561:Pseudoxanthoma Elasticum / Q000235:genetics / Q000503:physiopathology*; D012164:Retinal Diseases / Q000235:genetics / Q000503:physiopathology*; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000503:physiopathology; D014794:Visual Fields
D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human