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Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

Srilekha S, Arokiasamy T, Srikrupa NN, Umashankar V, Meenakshi S, Sen P, Kapur S, Soumittra N - PLoS ONE (2015)

Bottom Line: Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK.In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved.The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

View Article: PubMed Central - PubMed

Affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India; Ph.D Scholar, Birla Institute of Technology & Science (BITS), Hyderabad, India.

ABSTRACT
Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

No MeSH data available.


Related in: MedlinePlus

Segregation analysis.1a:arRP1 MERTK c.721C>T, 1b:LCA-1 RPE65 c.850+1G>T, 1c: LCA-2 CRB1 c.3307G>A, 1d:LCA-3 GUCY2D c.994delC, 1e:LCA-4 IQCB1 c.1278+6T>A, 1f:LCA-5 AIPL1 c.824G>A, 1g: LCA-7 RDH12 c.344-8C>T, 1h:LCA-8 AIPL1 c.247G>A, 1i:LCA-9 RPE65 c.1409C>T, 1j:LCA-10 AIPL1 c.613_622 delATCATCTGCC, 1k:LCA-11 SPATA7 c.913-2A>G. The arrow indicates the index case. The filled in circles and squares are affected females and males respectively. [M];[M]–affected with homozygous mutation, [M]; [=] –carries for any given mutation and [=]; [=] –wild type. Lines above the individual indicate availability of genotype.
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pone.0131679.g001: Segregation analysis.1a:arRP1 MERTK c.721C>T, 1b:LCA-1 RPE65 c.850+1G>T, 1c: LCA-2 CRB1 c.3307G>A, 1d:LCA-3 GUCY2D c.994delC, 1e:LCA-4 IQCB1 c.1278+6T>A, 1f:LCA-5 AIPL1 c.824G>A, 1g: LCA-7 RDH12 c.344-8C>T, 1h:LCA-8 AIPL1 c.247G>A, 1i:LCA-9 RPE65 c.1409C>T, 1j:LCA-10 AIPL1 c.613_622 delATCATCTGCC, 1k:LCA-11 SPATA7 c.913-2A>G. The arrow indicates the index case. The filled in circles and squares are affected females and males respectively. [M];[M]–affected with homozygous mutation, [M]; [=] –carries for any given mutation and [=]; [=] –wild type. Lines above the individual indicate availability of genotype.

Mentions: Segregation analysis (Fig 1a–1k) was performed in all the families and the mutation segregated within the family, with all the affected being homozygous for mutation, parent(s) being heterozygous carriers and the unaffected being either heterozygous for mutation or wild type. One hundred normal controls (200 chromosomes) were screened for the identified mutations and all were wild type.


Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families.

Srilekha S, Arokiasamy T, Srikrupa NN, Umashankar V, Meenakshi S, Sen P, Kapur S, Soumittra N - PLoS ONE (2015)

Segregation analysis.1a:arRP1 MERTK c.721C>T, 1b:LCA-1 RPE65 c.850+1G>T, 1c: LCA-2 CRB1 c.3307G>A, 1d:LCA-3 GUCY2D c.994delC, 1e:LCA-4 IQCB1 c.1278+6T>A, 1f:LCA-5 AIPL1 c.824G>A, 1g: LCA-7 RDH12 c.344-8C>T, 1h:LCA-8 AIPL1 c.247G>A, 1i:LCA-9 RPE65 c.1409C>T, 1j:LCA-10 AIPL1 c.613_622 delATCATCTGCC, 1k:LCA-11 SPATA7 c.913-2A>G. The arrow indicates the index case. The filled in circles and squares are affected females and males respectively. [M];[M]–affected with homozygous mutation, [M]; [=] –carries for any given mutation and [=]; [=] –wild type. Lines above the individual indicate availability of genotype.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493089&req=5

pone.0131679.g001: Segregation analysis.1a:arRP1 MERTK c.721C>T, 1b:LCA-1 RPE65 c.850+1G>T, 1c: LCA-2 CRB1 c.3307G>A, 1d:LCA-3 GUCY2D c.994delC, 1e:LCA-4 IQCB1 c.1278+6T>A, 1f:LCA-5 AIPL1 c.824G>A, 1g: LCA-7 RDH12 c.344-8C>T, 1h:LCA-8 AIPL1 c.247G>A, 1i:LCA-9 RPE65 c.1409C>T, 1j:LCA-10 AIPL1 c.613_622 delATCATCTGCC, 1k:LCA-11 SPATA7 c.913-2A>G. The arrow indicates the index case. The filled in circles and squares are affected females and males respectively. [M];[M]–affected with homozygous mutation, [M]; [=] –carries for any given mutation and [=]; [=] –wild type. Lines above the individual indicate availability of genotype.
Mentions: Segregation analysis (Fig 1a–1k) was performed in all the families and the mutation segregated within the family, with all the affected being homozygous for mutation, parent(s) being heterozygous carriers and the unaffected being either heterozygous for mutation or wild type. One hundred normal controls (200 chromosomes) were screened for the identified mutations and all were wild type.

Bottom Line: Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK.In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved.The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

View Article: PubMed Central - PubMed

Affiliation: SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India; Ph.D Scholar, Birla Institute of Technology & Science (BITS), Hyderabad, India.

ABSTRACT
Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 - 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

No MeSH data available.


Related in: MedlinePlus