Application of WES Towards Molecular Investigation of Congenital Cataracts : Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India
Congenital cataracts are the prime cause for irreversible blindness in children. The global incidence of congenital cataract is 2.2-13.6 per 10,000 births, with the highest prevalence in Asia. Nearly half of the congenital cataracts are of familial nature, with a predominant autosomal dominant pattern of inheritance. Over 38 of the 45 mapped loci for isolated congenital or infantile cataracts have been associated with a mutation in a specific gene. The clinical and genetic heterogeneity of congenital cataracts makes the molecular diagnosis a bit of a complicated task. Hence, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 11 pedigrees affected with familial congenital cataracts. Analysis of the WES data for known cataract genes identified causative mutations in six pedigrees (55%) in PAX6, FYCO1 (two variants), EPHA2, P3H2,TDRD7 and an additional likely causative mutation in a novel gene NCOA6, which represents the first dominant mutation in this gene. This study identifies a novel cataract gene not yet linked to human disease. NCOA6 is a transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
International journal of molecular sciences - 21(2020), 24 vom: 16. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kandaswamy, Dinesh Kumar [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2021 Date Revised 04.12.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms21249569 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319041778 |
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| 100 | 1 | |a Kandaswamy, Dinesh Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Application of WES Towards Molecular Investigation of Congenital Cataracts |b Identification of Novel Alleles and Genes in a Hospital-Based Cohort of South India |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 15.03.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Congenital cataracts are the prime cause for irreversible blindness in children. The global incidence of congenital cataract is 2.2-13.6 per 10,000 births, with the highest prevalence in Asia. Nearly half of the congenital cataracts are of familial nature, with a predominant autosomal dominant pattern of inheritance. Over 38 of the 45 mapped loci for isolated congenital or infantile cataracts have been associated with a mutation in a specific gene. The clinical and genetic heterogeneity of congenital cataracts makes the molecular diagnosis a bit of a complicated task. Hence, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 11 pedigrees affected with familial congenital cataracts. Analysis of the WES data for known cataract genes identified causative mutations in six pedigrees (55%) in PAX6, FYCO1 (two variants), EPHA2, P3H2,TDRD7 and an additional likely causative mutation in a novel gene NCOA6, which represents the first dominant mutation in this gene. This study identifies a novel cataract gene not yet linked to human disease. NCOA6 is a transcriptional coactivator that interacts with nuclear hormone receptors to enhance their transcriptional activator function | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a genetic heterogeneity | |
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| 700 | 1 | |a Prakash, Makarla Venkata Sathya |e verfasserin |4 aut | |
| 700 | 1 | |a Graw, Jochen |e verfasserin |4 aut | |
| 700 | 1 | |a Koller, Samuel |e verfasserin |4 aut | |
| 700 | 1 | |a Magyar, István |e verfasserin |4 aut | |
| 700 | 1 | |a Tiwari, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Berger, Wolfgang |e verfasserin |4 aut | |
| 700 | 1 | |a Santhiya, Sathiyaveedu Thyagarajan |e verfasserin |4 aut | |
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