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| [PMID]: | 28418495 |
| [Au] Autor: | Chen J; Wang Q; Cabrera PE; Zhong Z; Sun W; Jiao X; Chen Y; Govindarajan G; Naeem MA; Khan SN; Ali MH; Assir MZ; Rahman FU; Qazi ZA; Riazuddin S; Akram J; Riazuddin SA; Hejtmancik JF |
| [Ad] Endereço: | Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States 2Department of Ophthalmology, Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. |
| [Ti] Título: | Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive Congenital Cataracts by Homozygosity Screening. |
| [So] Source: | Invest Ophthalmol Vis Sci;58(4):2207-2217, 2017 Apr 01. | | [Is] ISSN: | 1552-5783 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Purpose: To identify the genetic origins of autosomal recessive congenital cataracts (arCC) in the Pakistani population. Methods: Based on the hypothesis that most arCC patients in consanguineous families in the Punjab areas of Pakistan should be homozygous for causative mutations, affected individuals were screened for homozygosity of nearby highly informative microsatellite markers and then screened for pathogenic mutations by DNA sequencing. A total of 83 unmapped consanguineous families were screened for mutations in 33 known candidate genes. Results: Patients in 32 arCC families were homozygous for markers near at least 1 of the 33 known CC genes. Sequencing the included genes revealed homozygous cosegregating sequence changes in 10 families, 2 of which had the same variation. These included five missense, one nonsense, two frame shift, and one splice site mutations, eight of which were novel, in EPHA2, FOXE3, FYCO1, TDRD7, MIP, GALK1, and CRYBA4. Conclusions: The above results confirm the usefulness of homozygosity mapping for identifying genetic defects underlying autosomal recessive disorders in consanguineous families. In our ongoing study of arCC in Pakistan, including 83 arCC families that underwent homozygosity mapping, 3 mapped using genome-wide linkage analysis in unpublished data, and 30 previously reported families, mutations were detected in approximately 37.1% (43/116) of all families studied, suggesting that additional genes might be responsible in the remaining families. The most commonly mutated gene was FYCO1 (14%), followed by CRYBB3 (5.2%), GALK1 (3.5%), and EPHA2 (2.6%). This provides the first comprehensive description of the genetic architecture of arCC in the Pakistani population. |
| [Mh] Termos MeSH primário: |
Catarata/congênito
Genes Recessivos/genética
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| [Mh] Termos MeSH secundário: |
Catarata/genética
Códon sem Sentido/genética
Feminino
Mutação da Fase de Leitura/genética
Marcadores Genéticos/genética
Homozigoto
Seres Humanos
Escore Lod
Masculino
Mutação de Sentido Incorreto/genética
Paquistão
Linhagem
Isoformas de Proteínas/genética
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Codon, Nonsense); 0 (Genetic Markers); 0 (Protein Isoforms) |
| [Em] Mês de entrada: | 1704 |
| [Cu] Atualização por classe: | 170426 |
[Lr] Data última revisão:
| 170426 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170419 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1167/iovs.17-21469 |
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