{"doi":"10.1002/ajmg.a.32634","title":"Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: The pitfalls of homozygosity mapping","abstract":"<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>CRB1</jats:italic> gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of <jats:italic>RDH12</jats:italic> 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.</jats:p>","journal":"American Journal of Medical Genetics Part A","year":2009,"id":631295,"datarank":0.5533319181170905,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":0.0,"self_endowment_contribution":0.5533319181170905,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1070636,"name":"Ronen Spiegel","orcid":"0000-0002-0108-4184","position":1,"is_corresponding":false},{"id":1635955,"name":"Noa Auslender","orcid":null,"position":2,"is_corresponding":false},{"id":1635958,"name":"Anan H Abbasi","orcid":null,"position":3,"is_corresponding":false},{"id":1411930,"name":"Leah Rizel","orcid":null,"position":4,"is_corresponding":false},{"id":1635963,"name":"Yasir Hujeirat","orcid":null,"position":5,"is_corresponding":false},{"id":1635966,"name":"Ihsan Salama","orcid":null,"position":6,"is_corresponding":false},{"id":1635967,"name":"Hanna J. 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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 <jats:italic>CRB1</jats:italic> gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of <jats:italic>RDH12</jats:italic> 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.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19140180","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fajmg.a.32634","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajmg.a.32634","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Humans","Retinal Degeneration","Alcohol Oxidoreductases","Eye Proteins","Membrane Proteins","Nerve Tissue Proteins","DNA Primers","Chromosome Mapping","Pedigree","DNA Mutational Analysis","Age of Onset","Consanguinity","Amino Acid Sequence","Base Sequence","Sequence Homology, Amino Acid","Haplotypes","Heterozygote","Homozygote","Genes, Recessive","Phenotype","Alleles","Molecular Sequence Data","Adolescent","Adult","Middle Aged","Child","Child, Preschool","Infant","Arabs","Israel","Female","Male"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T23:15:30.014612Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}