Clinical phenotype in a Swedish family with a mutation in the IMPDH1 gene.
OBJECTIVE
Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) have recently been discovered to cause a form of autosomal dominant retinitis pigmentosa (adRP). Such mutations are estimated to account for approximately 2-5% of the adRP cases among Americans of European origin and Europeans. Aiming towards an understanding of the molecular background of retinitis pigmentosa, this paper describes the phenotype of a Swedish family with a mutation in IMPDH1.


METHODS
Venous blood samples were obtained from 12 family members and screened for mutations in IMPDH1. Six individuals with the mutation were examined clinically and with full-field electroretinography (ERG), dark adaptometry, multifocal electroretinography (mfERG), and optical coherence tomography (OCT). Also reviewed were the clinical findings and ERGs obtained 14 years earlier.


RESULTS
The proband and eight other relatives from three generations were found to harbor the Asp226Asn mutation in IMPDH1. These individuals, from three generations, showed clinical and electrophysiological signs of retinitis pigmentosa. The cone responses to the full-field, 30-Hz flicker ERG demonstrated an unusual pattern, with implicit times within normal limits or only slightly prolonged. Rod ERG responses, however, were undetectable. OCT showed intraretinal fluid and swelling, changes that were more pronounced in younger individuals. mfERG showed residual preserved central function. The older the individual, the smaller the area of preserved central function.


CONCLUSIONS
In this family with a mutation in IMPDH1, we found a specific phenotype with rod function affected more than cone function, foveal edema, and central retinal function preserved for a long period of time. Foveal edema could be a pathogenic feature in this form of retinal degeneration.
Schatz
Patrik
P
Department of Ophthalmology, Lund University Hospital, Lund, Sweden. patrik.schatz@telia.com
Ponjavic
Vesna
V
Andréasson
Sten
S
McGee
Terri L
TL
Dryja
Thaddeus P
TP
Abrahamson
Magnus
M
D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D013548:Sweden; D041623:Tomography, Optical Coherence
D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human