Cone-rod dystrophy and a frameshift mutation in the PROM1 gene.
OBJECTIVE
To identify the genetic cause underlying autosomal recessive cone-rod dystrophy (CORD) and high myopia.


METHODS
Nine members of a consanguineous Arab family were clinically examined and were given fluorescein angiography (FA), biometry, and full field electroretinogram (ERG) testing. Blood samples were collected for DNA extraction. A homozygousity genome-wide scan was performed using >382 polymorphic microsatellite markers on genomic DNA from three affected family members. Regions of homozygosity were further analyzed in all members of the family. Mutation analysis of the PROM1 gene was performed by direct sequencing of PCR-amplified exons.


RESULTS
The phenotype is characterized by severe visual impairment evident in the first decade of life. Affected family members have bull;s-eye macular appearance, peripheral retinal pigment clumps, and cone-rod type ERG changes. Additionally, they have high myopia with axial lengths exceeding 25.3 mm. A genome-wide scan detected a region of 2.1 Mb on chromosome 4p that fully segregates with the disease within the family. This region encompasses the PROML1 gene, mutations of which have been implicated in retinal dystrophies. PROML1 mutation analysis identified a novel single nucleotide insertion at position 1629 of the cDNA resulting in truncation of approximately one-third of the protein.


CONCLUSIONS
The mutation described in this report further expands the clinical spectrum of PROM1 mutations.
Pras
Eran
E
Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin, 70300, Israel. eranpras@gmail.com
Abu
Almogit
A
Rotenstreich
Ygal
Y
Avni
Isaac
I
Reish
Orit
O
Morad
Yair
Y
Reznik-Wolf
Haike
H
Pras
Elon
E
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D020090:Chromosome Segregation / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005190:Family; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010455:Peptides / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides