Linked Life Data

20604683

Source:http://linkedlifedata.com/resource/pubmed/id/20604683

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-14
pubmed:abstractText
The history of the North African Jewish community is ancient and complicated with a number of immigration waves and persecutions dramatically affecting its population size. A decade-long process in Israel of clinical-molecular screening of North African Jews with incurable autosomal recessive blindness led to the identification of a homozygous splicing mutation (c.95-2A?>?T; IVS2-2A?>?T) in RPE65, the gene encoding the isomerase that catalyzes a key step in the retinoid-visual cycle, in patients from 10 unrelated families. A total of 33 patients (four now deceased) had the severe childhood blindness known as Leber congenital amaurosis (LCA), making it the most common cause of retinal degeneration in this population. Haplotype analysis in seven of the patients revealed a shared homozygous region, indicating a population-specific founder mutation. The age of the RPE65 founder mutation was estimated to have emerged 100-230 (mean, 153) generations ago, suggesting it originated before the establishment of the Jewish community in North Africa. Individuals with this RPE65 mutation were characterized with retinal studies to determine if they were candidates for gene replacement, the recent and only therapy to date for this otherwise incurable blindness. The step from molecular anthropological studies to application of genetic medicine was then taken, and a representative of this patient subgroup was treated with subretinal rAAV2-RPE65 gene therapy. An increase in vision was present in the treated area as early as 15 days after the intervention. This process of genetically analyzing affected isolated populations as a screen for gene-based therapy suggests a new paradigm for disease diagnosis and treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1557-7422
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1749-57
pubmed:meshHeading
pubmed-meshheading:20604683-Adolescent, pubmed-meshheading:20604683-Adult, pubmed-meshheading:20604683-Africa, Northern, pubmed-meshheading:20604683-Base Sequence, pubmed-meshheading:20604683-Carrier Proteins, pubmed-meshheading:20604683-Child, pubmed-meshheading:20604683-Child, Preschool, pubmed-meshheading:20604683-Dependovirus, pubmed-meshheading:20604683-Eye Proteins, pubmed-meshheading:20604683-Female, pubmed-meshheading:20604683-Gene Therapy, pubmed-meshheading:20604683-Genetic Vectors, pubmed-meshheading:20604683-Genotype, pubmed-meshheading:20604683-Humans, pubmed-meshheading:20604683-Israel, pubmed-meshheading:20604683-Leber Congenital Amaurosis, pubmed-meshheading:20604683-Male, pubmed-meshheading:20604683-Middle Aged, pubmed-meshheading:20604683-Mutation, pubmed-meshheading:20604683-Pedigree, pubmed-meshheading:20604683-Photic Stimulation, pubmed-meshheading:20604683-Photoreceptor Cells, Vertebrate, pubmed-meshheading:20604683-Polymorphism, Single Nucleotide, pubmed-meshheading:20604683-RNA Splice Sites, pubmed-meshheading:20604683-Retina, pubmed-meshheading:20604683-Vision Tests, pubmed-meshheading:20604683-Young Adult
pubmed:year
2010
pubmed:articleTitle
Molecular anthropology meets genetic medicine to treat blindness in the North African Jewish population: human gene therapy initiated in Israel.
pubmed:affiliation
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. banine@cc.huji.ac.il
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't