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Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: The pitfalls of homozygosity mapping
Author(s) -
Benayoun Liat,
Spiegel Ronen,
Auslender Noa,
Abbasi Anan H,
Rizel Leah,
Hujeirat Yasir,
Salama Ihsan,
Garzozi Hanna J.,
AllonShalev Stavit,
BenYosef Tamar
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32634
Subject(s) - disease gene identification , genetics , genetic heterogeneity , retinal degeneration , biology , mutation , gene , phenotype , exome sequencing
Retinitis pigmentosa is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4,000. At least 28 genes and loci have been implicated in nonsyndromic autosomal recessive retinitis pigmentosa. Here we report two extended and highly consanguineous families segregating early onset retinitis pigmentosa. Despite the consanguinity in both families, we found allelic heterogeneity in one of them, in which affected individuals were compound heterozygotes for two different mutations of the CRB1 gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of RDH12 was found in only 14 of 17 affected individuals in this family. Our data indicate that in the other affected individuals the disease is caused by a different gene/s. These findings demonstrate that while homozygosity mapping is an efficient tool for identification of the underlying mutated genes in inbred families, both locus and allelic heterogeneity may occur even within the same consanguineous family. These observations should be taken into account, especially when studying common and heterogeneous recessive genetic conditions. © 2009 Wiley‐Liss, Inc.