Molecular testing for hereditary retinal disease as part of clinical care.
OBJECTIVE
To describe clinical molecular testing for hereditary retinal degenerations, highlighting results, interpretation, and patient education.


METHODS
Mutation analysis of 8 retinal genes was performed by dideoxy sequencing. Pretest and posttest genetic counseling was offered to patients. The laboratory report listed results and provided individualized interpretation.


RESULTS
A total of 350 tests were performed. The molecular basis of disease was determined in 133 of 266 diagnostic tests; the disease-causing mutations were not identified in the remaining 133 diagnostic tests. Predictive and carrier tests were requested for 9 and 75 nonsymptomatic patients with known familial mutations, respectively.


CONCLUSIONS
Molecular testing can confirm a clinical diagnosis, identify carrier status, and confirm or rule out the presence of a familial mutation in nonsymptomatic at-risk relatives. Because causative mutations cannot be identified in all patients with retinal diseases, it is essential that patients are counseled before testing regarding the benefits and limitations of this emerging diagnostic tool.


CONCLUSIONS
The molecular definition of the genetic basis of disease provides a unique adjunct to the clinical care of patients with hereditary retinal degenerations.
Downs
Katy
K
Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Zacks
David N
DN
Caruso
Rafael
R
Karoukis
Athanasios J
AJ
Branham
Kari
K
Yashar
Beverly M
BM
Haimann
Mark H
MH
Trzupek
Karmen
K
Meltzer
Meira
M
Blain
Delphine
D
Richards
Julia E
JE
Weleber
Richard G
RG
Heckenlively
John R
JR
Sieving
Paul A
PA
Ayyagari
Radha
R
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000075002:Bestrophins; D002648:Child; D018118:Chloride Channels; D003094:Collagen / Q000235:genetics; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D010353:Patient Education as Topic; D064531:Peripherins; D012162:Retinal Degeneration / Q000235:genetics*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C113133:BEST1 protein, human; D000075002:Bestrophins; C487851:C1QTNF5 protein, human; D018118:Chloride Channels; C119630:EFEMP1 protein, human; C418975:ELOVL4 protein, human; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064531:Peripherins; C108726:RS1 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D003094:Collagen