TY - JOUR
T1 - Identification of mutations causing inherited retinal degenerations in the Israeli and Palestinian populations using homozygosity mapping
AU - Beryozkin, Avigail
AU - Zelinger, Lina
AU - Bandah-Rozenfeld, Dikla
AU - Shevach, Elia
AU - Harel, Anat
AU - Storm, Tim
AU - Sagi, Michal
AU - Eli, Dalia
AU - Merin, Saul
AU - Banin, Eyal
AU - Sharon, Dror
PY - 2014/1/28
Y1 - 2014/1/28
N2 - Methods. Clinical analysis included family history, ocular examination, full-field electroretinography (ERG), and funduscopy. Molecular analysis included homozygosity mapping and mutation analysis of candidate genes. Results. We recruited for the study families with AR nonsyndromic retinal degenerations, including mainly retinitis pigmentosa (RP), cone-rod degeneration (CRD), and Leber congenital amaurosis (LCA). With the aim to identify the causative genes in these families, we performed homozygosity mapping using whole genome single nucleotide polymorphism (SNP) arrays in 125 families. The analysis revealed the identification of 14 mutations, 5 of which are novel, in 16 of the families. The mutations were identified in the following eight genes: RDH12, PROM1, MFRP, TULP1, LCA5, CEP290, NR2E3, and EYS. While most patients had a retinal disease that is compatible with the causing gene, in some cases new clinical features are evident. Conclusions. Homozygosity mapping is a powerful tool to identify genetic defects underlying heterogeneous AR disorders, such as RP and LCA, in consanguineous and nonconsanguineous patients. The identification of significant and large homozygous regions, which do not include any known retinal disease genes, may be a useful tool to identify novel disease-causing genes, using next generation sequencing.
AB - Methods. Clinical analysis included family history, ocular examination, full-field electroretinography (ERG), and funduscopy. Molecular analysis included homozygosity mapping and mutation analysis of candidate genes. Results. We recruited for the study families with AR nonsyndromic retinal degenerations, including mainly retinitis pigmentosa (RP), cone-rod degeneration (CRD), and Leber congenital amaurosis (LCA). With the aim to identify the causative genes in these families, we performed homozygosity mapping using whole genome single nucleotide polymorphism (SNP) arrays in 125 families. The analysis revealed the identification of 14 mutations, 5 of which are novel, in 16 of the families. The mutations were identified in the following eight genes: RDH12, PROM1, MFRP, TULP1, LCA5, CEP290, NR2E3, and EYS. While most patients had a retinal disease that is compatible with the causing gene, in some cases new clinical features are evident. Conclusions. Homozygosity mapping is a powerful tool to identify genetic defects underlying heterogeneous AR disorders, such as RP and LCA, in consanguineous and nonconsanguineous patients. The identification of significant and large homozygous regions, which do not include any known retinal disease genes, may be a useful tool to identify novel disease-causing genes, using next generation sequencing.
KW - Homozygosity mapping
KW - Retinal degeneration
KW - Retinitis pigmentosa
UR - http://www.scopus.com/inward/record.url?scp=84894465581&partnerID=8YFLogxK
U2 - 10.1167/iovs.13-13625
DO - 10.1167/iovs.13-13625
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C2 - 24474277
AN - SCOPUS:84894465581
SN - 0146-0404
VL - 55
SP - 1149
EP - 1160
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -